![Transcription factories in a Hela cell [from Cook PR (1999) Science 284, 1790]](../images/pombo.png)
Updated on 21 November, 2016
Simple regulatory circuits in bacteria and
yeast
Box 6-1. Positive and
negative control in the lac operon
Box 6-2. A complex
circuit involving the lambda repressor
Box. Riboswitches
Principles of eukaryotic gene regulation
Most
cells in an organism contain the same DNA
Box. Embryonic
stem cells (new section)
Box 6-3. Sequence
changes in antibody genes
Different levels of control
Box
6-4. Gene amplification
Box 6-5. Inheritance of
methylated sequences in DNA
Box 6-6. Alternative promoters,
splicing, and polyadenylation
Box. RNA editing (new
section)
Box. Ribozymes (new section)
Epigenetic regulation
Localizing
transcripts to specific regions
Non-genic
transcription
Box 6-7. Co-suppression and
RNA interference
Inheriting the differentiated state through
mitosis
Differential
expression can require continuous regulation
Monoallelic expression
Box 6-8. Identification of
MyoD, a myogenic transactivator
Relative
expression levels in different cells
Box 6-9. Designing a
eukaryotic repressor
Regulation at the level of the nucleosome
Nucleosome
positioning and modification
Chromatin remodeling
Regulation at the level of the loop
Box 6-10. Defining DNA
motifs that regulate transcription
Heterochromatin
Effects at the periphery
Silencing in yeast
DNA
methylation in vertebrates
Polycomb
proteins of Drosophila
Establishing and inheriting patterns of
expression
Example:
inheriting activity of rDNA genes
Example:
anterior-posterior patterning in Drosophila eggs
Box 6-11. Maternal-effect
genes in Drosophila
Example:
commitment of hematopoietic stem cells
Example:
converting fibroblasts into ES-like cells
Control of nuclear import and export
Example: HIV/RevRRE
Example: p53
Example: Relocating a transcription factor
mRNA localization
Zip-codes
Some examples
mRNA turnover
mRNA levels do not necessarily reflect the translation rate
Decapping and deadenylation
Nonsense-mediated decay; does some occur in the nucleus?
Decapping and decay occur in cytoplasmic processing bodies
RNAi
Regulation at the ribosome
mRNA and amino acid supply
Translation factors
Regulatory motifs at each end of the mRNA
Example: Some tricks played by viruses
Protein modification and turnover
Cotranslational modification of proteins
Regulated protein degradation
Box. Inteins
Heritable changes in protein structure - prions
How cells know where they are
Simple regulatory
circuits in bacteria and
yeast
Figure: 6-1.
Reference:
Engelsberg, E. and Wilcox, G. (1974). Regulation: positive
control.
Annu Rev. Genet. 8, 219-242.
Sigler, P.B. (1992). The molecular mechanism of trp repression.
In 'Transcriptional regulation'. Eds S.L. McKnight and K.R. Yamamoto.
Cold Spring Harbor Laboratory Press; Cold Spring Harbor, NY.
Ptashne, M. (1997). Control of gene transcription: an outline.
Nat.
Med. 3, 1069-1072.
Ptashne, M. and Gann, A. (1997). Transcriptional activation by
recruitment. Nature 386, 569-577. [PubMed]
Additional reference:
Ptashne, M. (2009). Binding reactions: epigenetic switches, signal transduction and cancer. Curr. Biol. 19, R234-241. [PubMed]
Ptashne, M. (2011). Principles of a switch. Nat. Chem. Biol. 7, 484-487.
[PubMed]
Box 6-1. Positive
and negative control in the lac operon
Figure: 6-2.
Reference:
Gottesman, S. (1984). Bacterial regulation: global regulatory networks.
Annu Rev. Genet. 18, 415-442.
Additional reference:
Wilson, C.J., Zhan, H., Swint-Kruse, L., and Matthews, K.S. (2007). The lactose repressor system: paradigms for regulation, allosteric behavior and protein folding. Cell. Mol. Life Sci. 64, 3-16. [PubMed]
Box 6-2. A complex
circuit involving the
lambda repressor
Figure: 6-3.
Reference:
Ptashne, M. (2004). 'Genetic switch; phage lambda revisited''. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y..
Additional reference:
Ptashne, M. (2009). Binding reactions: epigenetic switches, signal transduction and cancer. Curr. Biol. 19, R234-241. [PubMed]
Box. Riboswitches
Additional reference:
Serganov, A. (2009). The long and the short of riboswitches. Curr. Opin. Struct. Biol. 19, 251-259. [PubMed]
Principles of
eukaryotic gene regulation
Additional reference:
Biggin, M.D. (2011). Animal transcription networks as highly connected, quantitative continua. Dev. Cell 21, 611-626. [PubMed]
Graf, T., and Enver, T. (2009). Forcing cells to change lineages. Nature 462, 587-594. [PubMed]
Hager, G.L., McNally, J.G., and Misteli, T. (2009). Transcription dynamics. Mol. Cell 35, 741-753. [PubMed]
Losick, R., and Desplan, C. (2008). Stochasticity and cell fate. Science 320, 65-88. [PubMed]
Lenhard, B., Sandelin, A., and Carninci, P. (2012). Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat. Rev. Genet. 13, 233-245.
[PubMed]
Orphanides, G. and Reinberg, D. (2002). A unified theory
of gene expression. Cell 108, 439-451. [PubMed]
Most
cells in an organism contain the same DNA
Figure: 6-4.
Reference:
Colman, A. (2000). Somatic cell nuclear transfer in mammals: progress
and applications. Cloning 1, 185-200.
Gurdon, J.B. and Colman, A. (1999). The future of cloning. Nature 402,
743-746.
Wilmut, I., Schneike, A.E., McWhir, J., Kind, A.J. and Campbell, K.H.S.
(1997). Viable offspring derived from fetal and adult mammalian cells.
Nature 385, 810-813. [PubMed]
Additional reference:
Biesecker, L.G., and Spinner, N.B. (2013). A genomic view of mosaicism and human disease. Nat. Rev. Genet. 14, 307-320. [PubMed]
Buganim, Y., Faddah, D.A., and Jaenisch, R. (2013). Mechanisms and models of somatic cell reprogramming. Nat. Rev. Genet. 14, 427-439. [PubMed]
Jullien, J., Pasque, V., Halley-Stott, R.P., Miyamoto, K., and Gurdon, J.B. (2011). Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process? Nat. Rev. Mol. Cell Biol. 12, 453-459. [PubMed]
Wang, J., Mitreva, M., Berriman, M., Thorne, A., Magrini, V., Koutsovoulos, G., Kumar, S., Blaxter, ML., and Davis, R.E. (2012). Silencing of germline-expressed genes by DNA elimination in somatic cells. Dev. Cell 23, 1072-1080. [PubMed]
Yamanaka, S., and Blau, H. ( 2010). Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704-712. [PubMed]
Box. Embryonic stem cells (new section)
Reference:
Anokye-Danso, F., Trivedi, C.M., Juhr, D., Gupta, M., Cui, Z., Tian, Y., Zhang, Y., Yang, W., Gruber, P.J., Epstein, J.A., and Morrisey, E.E. (2011). Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8, 376-888. [PubMed]
de Souza, N. (2010). Primer: induced pluripotency. Nat. Methods 7, 20-21. [PubMed]
Graf, T., and Enver, T. (2009). Forcing cells to change lineages. Nature 462, 587-594. [PubMed]
Gurdon, J.B., and Melton, D.A. (2008). Nuclear reprogramming in cells. Science 322, 1811-1815. [PubMed]
Magnúsdóttir E., and Surani M.A. (2014). How to make a primordial germ cell. Development 141, 245-252. [PubMed]
Stadtfeld, M., and Hochedlinger, K. (2010). Induced pluripotency: history, mechanisms, and applications. Genes Dev 24, 2239-2263. [PubMed]
Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676. [PubMed]
Yamanaka, S., and Blau, H. ( 2010). Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704-712. [PubMed]
Web link:
http://learn.genetics.utah.edu/content/tech/stemcells/ Primer from the University of Utah.
Box 6-3. Sequence
changes in antibody genes
Figure: 6-5.
Reference:
Alt, F.W., Blackwell, T.K. and Vancopoulos, G.D. (1987).
Development of the primary antibody repertoire. Science 238,
1079-1087. [PubMed]
Additional reference:
Perlot, T., and Alt, F.W. (2008). Cis-regulatory elements and epigenetic changes control genomic rearrangements of the IgH locus. Adv. Immunol. 99, 1-32. [PubMed]
Different
levels of control
Additional reference:
Balagopal, V., and Parker, R. (2009). Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr. Opin. Cell Biol. 21, 403-408. [PubMed]
Biggin, M.D. (2011). Animal transcription networks as highly connected, quantitative continua. Dev. Cell 21, 611-626. [PubMed]
Groppo, R., and Richter, J.D. (2009). Translational control from head to tail. Curr. Opin. Cell Biol. 21, 444-451. [PubMed]
Lenhard, B., Sandelin, A., and Carninci, P. (2012). Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat. Rev. Genet. 13, 233-245.
[PubMed]
Scott, W.G., Martick, M., and Chi, Y.I. (2009). Structure and function of regulatory RNA elements: ribozymes that regulate gene expression. Biochim. Biophys. Acta 1789, 634-641. [PubMed]
Sonenberg, N., and Hinnebusch, A.G. (2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731-745. [PubMed]
Swinburne, I.A., and Silver, P.A. (2008). Intron delays and transcriptional timing during development. Dev. Cell. 14, 324-330. [PubMed]
Taft, R.J., Pang, K.C., Mercer, T.R., Dinger, M., and Mattick, J.S. (2009). Non-coding RNAs: regulators of disease. J. Pathol. 220, 126-139
[PubMed]
Box
6-4. Gene amplification
Reference:
Long, E.O. and Dawid, I.B. (1980). Repeated genes in eucaryotes. Annu
Rev. Biochem. 49, 727-764.
Stark, G.R. and Wahl, G.M. (1984). Gene amplification. Annu Rev.
Biochem. 53, 447-491.
Additional reference:
Lee, H.O., Davidson, J.M., and Duronio, R.J. (2009). Endoreplication: polyploidy with purpose. Genes Dev. 23, 2461-2477. [PubMed]
Zhang, F., Gu W., Hurles, ME., and Lupski, J.R. (2009). Copy number variation in human health, disease, and evolution. Annu. Rev Genomics Human Genet. 10, 451-481. [PubMed]
Box
6-5. Inheritance of methylated sequences
in DNA
Reference:
McGhee, J.D. and Ginder, G.D. (1979). Specific DNA methylation sites in
the vicinity of the chicken β-globin genes.
Nature 280, 419-420.
Bird, A. (1992). The essentials of DNA methylation. Cell 70, 5-8.
Bird, A.P. and Wolffe, A.P. (1999). Methylation-induced repression -
belts, braces, and chromatin. Cell 99, 451-454.
Additional reference:
Bergman, Y., and Cedar, H. (2013). DNA methylation dynamics in health and disease. Nat. Struct. Mol. Biol. 20, 274-281. [PubMed]
Deaton, A.M., and Bird, A. (2011). CpG islands and the regulation of transcription. Genes Dev. 25, 1010-1022. [PubMed]
Ooi, S.K., O'Donnell, A.H., and Bestor, T.H. (2009). Mammalian cytosine methylation at a glance. J. Cell Sci. 122, 2787-2791. [PubMed]
Box
6-6. Alternative promoters, splicing, and
polyadenylation
Figure: 6-6.
Reference:
Sharp, P.A. (1994). Split genes and RNA splicing. Cell 77,
805-815.
Chabot, B. (1996). Directing alternative splicing: cast and scenarios.
Trends Genet. 12, 472-478. [PubMed]
Lenhard, B., Sandelin, A., and Carninci, P. (2012). Metazoan promoters: emerging characteristics and insights into transcriptional regulation. Nat. Rev. Genet. 13, 233-245.
[PubMed]
Schmucker, D., Clemens, J.C., Shu, H., Worby, C.A., Xiao, J., Muda, M.,
Dixon, J.E. and Zipursky, S.L. (2000). Drosophila Dscam is an
axon guidance receptor exhibiting extraordinary molecular diversity.
Cell 101, 671-684. [PubMed]
Additional reference:
Andreassi, C., and Riccio, A. (2009). To localize or not to localize: mRNA fate is in 3'UTR ends. Trends Cell Biol. 19, 465-474. [PubMed]
Kornblihtt, A.R., Schor, I.E., Alló, M., Dujardin, G., Petrillo, E., and Muñoz, M.J. (2013). Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat. Rev. Mol. Cell. Biol. 14, 153-165. [PubMed]
Schmucker, D., and Chen, B. (2009). Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes. Genes Dev 23, 147-156. [PubMed]
Box. RNA editing (new section)
Reference:
Farajollahi, S., and Maas, S. (2010). Molecular diversity through RNA editing: a balancing act. Trends Genet. 26, 221-230. [PubMed]
Box. Ribozymes (new section)
Reference:
Scott, W.G., Martick, M., and Chi, Y.I. (2009). Structure and function of regulatory RNA elements: ribozymes that regulate gene expression. Biochim. Biophys. Acta 1789, 634-641. [PubMed]
Epigenetic regulation (new section)
Additional reference:
Audergon, P.N., Catania, S., Kagansky, A., Tong, P., Shukla, M., Pidoux, A.L., and Allshire, R.C. (2015). Epigenetics. Restricted epigenetic inheritance of H3K9 methylation. Science 348, 132-135. [PubMed]
Feng, S., Jacobsen, S.E., and Reik, W. (2010). Epigenetic reprogramming in plant and animal development. Science 330, 622-627. [PubMed]
Heard, E., and Martienssen, R.A. (2014). Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95-109. [PubMed]
Henikoff, S., and Greally, J.M. (2016). Epigenetics, cellular memory and gene regulation. Curr. Biol. 26, R644-648. [PubMed]
Ptashne, M. (2013). Faddish stuff: epigenetics and the inheritance of acquired characteristics. FASEB J. 27, 1-2. [PubMed]
Web link:
http://learn.genetics.utah.edu/content/epigenetics/ Primer from the University of Utah.
Localizing transcripts to
specific
regions
For mRNA localization in the cytoplasm, see below.
Additional reference:
Parton, R.M., Davidson, A., Davis, I., and Weil, T.T. (2014). Subcellular mRNA localisation at a glance. J. Cell Sci. 127, 2127-2133. [PubMed]
Non-genic
transcription
Reference:
Thorey, I.S., Cecea, G., Reynolds, W. and Oshima, R.G. (1993). Alu sequence involvement in transcriptional insulation of
the keratin 18 gene in transgenic mice. Mol. Cell. Biol. 13,
6742-6751. [PubMed]
Gribnau, J., Diderich, K., Pruzina, S., Calzolari, R. and Fraser, P.
(2000). Intergenic transcription and developmental remodeling of
chromatin subdomains in the human β-globin locus. Mol. Cell 5, 377-386. [PubMed]
Reinhart, B.J., Slack, F.J., Basson, M., Pasquinelli, A.E., Bettinger,
J.C., Rougvie, A.E., Horvitz, H.R. and Ruvkun, G. (2000). The
21-nucleotide let-7 RNA regulates developmental timing in
Caenorhabditis elegans. Nature 403, 901-906. [PubMed]
Tracy, R.B. and Lieber, M.R. (2000). Transcription-dependent R-loop
formation at mammalian class switch sequences. EMBO J. 19,
1055-1067. [PubMed]
[Full
text]
Additional reference:
Cook, P.R. (2003). Nongenic transcription, gene regulation and
action at a distance. J. Cell Sci. 116, 4483-4491. [PubMed]
Djebali S., et al. (2012). Landscape of transcription in human cells. Nature 489, 101-108. [PubMed]
Esteller, M. (2011). Non-coding RNAs in human disease. Nat. Rev. Genet 12, 861-874. [PubMed]
Morris, K.V., and Mattick, J.S. (2014). The rise of regulatory RNA. Nat. Rev. Genet. 15, 423-437. [PubMed]
Web link:
http://biobases.ibch.poznan.pl/ncRNA/ Database of non-coding RNAs.
http://research.imb.uq.edu.au/rnadb/ Database of mammalian non-coding RNAs.
Box 6-7.
Co-suppression and RNA interference
Reference:
Bosher, J.M. and Labouesse, M. (2000). RNA interference:
a genetic wand and genetic watchdog. Nature Cell Biol. 2,
E31-E36. [PubMed]
Additional reference:
Fraser, A.G., Kamath, R.S., Zipperlon, P., Martinez-Campos, M.,
Sohrmann, M. and Ahringer, J. (2000). Functional genomic analysis of C.
elegans chromosome I by systematic RNA interference. Nature 408,
325-330. [PubMed]
Flamand, M., and Duchaine, T.F. (2012). SnapShot: Endogenous RNAi pathways. Cell 150, 442-442. [PubMed]
Grishok, A., Pasquinelli, A.E., Conte, D., Li, N., Parrish, S., Ha, I.,
Baillie, D.L., Fire, A., Ruvkun, G. and Mello, C.C. (2001). Genes and
mechanisms related to RNA interference regulate expression of the small
temporal RNAs that control C. elegans developmental timing.
Cell 106, 23-34. [PubMed]
Sulston, J.E., Schierenberg, J., White, J. and Thompson, N. (1983). The
embryonic cell lineage of the nematode Caenorhabditis elegans.
Dev. Biol. 100, 64-119. [PubMed]
Inheriting
the differentiated state through
mitosis
Figure: 6-7.
Reference:
Lyon, M.F. (1992). Some milestones in the history of X-chromosome
inactivation. Annu Rev. Genet. 26, 17-28.
Penny, G.D., Kay, G.F., Sheardown, S.A., Rastan, S. and Brockdorff, N.
(1996). Requirement for Xist in X chromosome inactivation.
Nature 379, 131-137. [PubMed]
Panning, B. and Jaenisch, R. (1998). RNA and the epigenetic regulation
of X chromosome inactivation. Cell 93, 305-308.
Additional reference:
Augui, S., Nora, E.P., and Heard, E. (2011). Regulation of X-chromosome inactivation by the X-inactivation centre. Nat. Rev. Genet. 12, 429-442. [PubMed]
Lee, J.T. (2011). Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control. Nat. Rev. Mol. Cell Biol. 12, 815-826. [PubMed]
Lee, J.T. (2012). Epigenetic regulation by long noncoding RNAs. Science 338, 1435-1439. [PubMed]
Zaidi, S.K., Young, D.W., Montecino, M.A., Lian, J.B., van Wijnen, A.J., Stein, J.L., and Stein, G.S. (2010). Mitotic bookmarking of genes: a novel dimension to epigenetic control. Nat. Rev. Genet. 11, 583-589. [PubMed]
Monoallelic expression
Reference:
Ohlsson, R. (2007). Widespread monoallelic expression. Science 318, 1077-1078. [PubMed]
Zakharova, I.S., Shevchenko, A.I., and Zakian, S.M. (2009). Monoallelic gene expression in mammals. Chromosoma 118, 279-290. [PubMed]
Differential
expression can require continuous
regulation
Reference:
Blau, H.M. (1994). Heterokaryons reveal that differentiation requires
continuous regulation. In 'The legacy of cell fusion', Ed. Gordon, S.
Oxford University Press, Oxford.
Additional reference:
Johnston, L.A. (2005). Regeneration and transdetermination: new
tricks from old cells. Cell 120,
288-290. [PubMed]
Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676. [PubMed]
Box
6-8. Identification of MyoD, a myogenic
transactivator
Reference:
Davis, R.L., Weintraub, H. and Lassar, A.B. (1987). Expression of a
single transfected cDNA converts fibroblasts to myoblasts. Cell 51,
987-1000. [PubMed]
Weintraub, H. (1993). The myoD family and myogenesis:
redundancy, networks and thresholds. Cell 75, 1241-1244.
Additional reference:
Bryson-Richardson, R.J., and Currie, P.D. (2008). The genetics of vertebrate myogenesis. Nat. Rev. Genet. 9, 632-646. [PubMed]
Cao, Y., Yao, Z., Sarkar, D., Lawrence, M., Sanchez, G.J., Parker, M.H., MacQuarrie, K.L., Davison, J., Morgan, M.T., Ruzzo, W.L., Gentleman, R.C., and Tapscott, S.J. (2010). Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev. Cell 18, 662-674. [PubMed]
Web link:
http://www.ucalgary.ca/UofC/eduweb/virtualembryo/muscle_determ-diffn.html Muscle development.
Relative expression
levels in different cells
Reference:
Ivarie, R.D., Schacter, B.S. and O'Farrell, P.H. (1983).
The level of expression of the rat growth hormone gene in liver tumour
cells is at least eight orders of magnitude less than that in anterior
pituitary cells. Mol. Cell Biol. 3, 1460-1467. [PubMed]
Box
6-9. Designing a eukaryotic repressor
Reference:
Ptashne, M. (1992). 'A genetic switch'. 2nd ed. Cell Press and
Blackwell Press, Cambridge, MA.
Regulation
at the level of the nucleosome
Figure: 6-8, 6-9.
Reference:
Stalder, J., Larsen, A., Engel, J.D., Dolan, M., Groudine, M. and
Weintraub, H. (1980). Tissue-specific DNA cleavages in the
globin chromatin domain induced by DNase I. Cell 20, 451-460.
Kornberg, R.D. and Lorch, Y. (1993). Nucleosome positioning. Nucl.
Acids Mol. Biol. 7, 217-225.
Wolffe, A. (1998). 'Chromatin: structure and function'. 3rd edition. Academic Press, London.
Additional reference:
Kimura, H. and Cook, P.R. (2001). Kinetics of core histones in living
human cells: little exchange of H3 and H4 and some rapid exchange of
H2B. J. Cell Biol. 153, 1341-1353. [PubMed]
[Full text]
Tessarz, P., and Kouzarides. T. (2014). Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol. 15, 703-708. [PubMed]
Nucleosome
positioning and modification
Reference:
Kornberg, R.D. and Lorch, Y. (1993). Nucleosome positioning. Nucl.
Acids Mol. Biol. 7, 217-225.
Wyrick, J.J., Hostege, F.C.P., Jennings, E.G., Causton, H.C., Shore,
D., Grunstein, M., Lander, E.S. and Young, R.A. (1999). Chromosomal
landscape of nucleosome-dependent gene expression and silencing in
yeast. Nature 402, 418-421. [PubMed]
Strahl, B.D. and Allis, C.D. (2000). The language of covalent histone
modifications. Nature 403, 41-45. [PubMed]
Additional reference:
Cubeñas-Potts, C., and Matunis, M.J. (2013). SUMO: a multifaceted modifier of chromatin structure and function. Dev Cell 24, 1-12. [PubMed]
Filion, G.J., van Bemmel, J.G., Braunschweig, U., Talhout, W., Kind, J., Ward, L.D., Brugman, W., de Castro, I.J., Henikoff, S., and Greally, J.M. (2016). Epigenetics, cellular memory and gene regulation. Curr. Biol. 26, R644-648. [PubMed]
Kerkhoven, R.M., Bussemaker, H.J., and van Steensel, B. (2010). Systematic protein location mapping reveals five principal chromatin types in Drosophila cells. Cell 143, 212-224. [PubMed]
Ling, X., Harkness, T.A., Schultz, M.C., Fisher-Adams, G., and Grunstein, M. (2006). Yeast histone H3 and H4 amino termini are important for nucleosome assembly in vivo and in vitro: redundant and position-independent functions in assembly but not in gene regulation. Genes Dev. 10, 686-699. [PubMed]
Struhl, K., and Segal, E. (2013). Determinants of nucleosome positioning. Nat. Struct. Mol. Biol. 20, 267-273. [PubMed]
Tessarz, P., and Kouzarides. T. (2014). Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol. 15, 703-708. [PubMed]
Zentner, G.E., and Henikoff, S. (2013). Regulation of nucleosome dynamics by histone modifications. Nat. Struct. Mol. Biol. 20, 259-266. [PubMed]
Web link:
http://jcs.biologists.org/cgi/content/full/116/11/2117 The histone code from 'Cell Science at a glance'.
http://download.cell.com/pdfs/0092-8674/PIIS0092867407014092.pdf Histone modifying enzymes.
Chromatin
remodeling
Reference:
Travers, A. (1999). An engine for nucleosome remodeling.
Cell 96, 311-314.
Vignali, M., Hassan, A.H., Neely, K.E. and Workman, J.L.
(2000). ATP-dependent chromatin-remodeling complexes. Mol. Cell.
Biol. 20, 1899-1910. [Full
text]
Additional reference:
Clapier, C.R., and Cairns, B.R. (2009). The biology of chromatin remodeling complexes. Annu, Rev. Biochem. 78, 273-304. [PubMed]
Kasten, M.M., Clapier, C.R., and Cairns, B.R. (2011). SnapShot: chromatin remodeling: SWI/SNF. Cell 144, 310. [PubMed]
Sims, J.K., and Wade, P.A. (2011). SnapShot: chromatin remodeling: CHD. Cell 144, 626-626. [PubMed]
Wu, J.I., Lessard, J., and Crabtree, G.R. (2009). Understanding the words of chromatin regulation. Cell 136, 200-206. [PubMed]
Yadon, A.N., and Tsukiyama, T. (2011). SnapShot: chromatin remodeling: ISWI. Cell 144, 453-453. [PubMed]
Web link:
http://jcs.biologists.org/cgi/content/full/117/17/3707?etoc Remodelling machines from 'Cell Science at a glance'.
Regulation
at the level of the loop
Figure: 6-10.
Reference:
Banerji, J., Rusconi, S. and Schaffner, W. (1981). Expression of the
b-globin gene is enhanced by remote SV40 DNA sequences. Cell 27,
299-308. [PubMed]
Grosveld, F., Assendelft, G.B. van, Greaves, D.R. and Kallios, G.
(1987). Position independent, high-level expression of the β-globin gene in
transgenic mice. Cell 51, 975-985. [PubMed]
Iborra, F.J., Pombo, A., McManus, J.,
Jackson, D.A. and Cook, P.R. (1996). The topology of transcription by
immobilized polymerases. Exp. Cell Res. 229, 167-173. [PubMed]
[Full
text]
Ishii, K., Arib, G., Lin, C., Van Houwe,
G. and Laemmli, U.K. (2002). Chromatin boundaries in budding yeast: the
nuclear pore connection. Cell 109, 551-562. [PubMed]
Engel, J.D. and Tanimoto, K. (2000).
Looping, linking, and chromatin activity: new insights into β-globin locus regulation. Cell 100,
499-502.
Additional reference:
Cook, P.R. (2010). A model for all genomes; the role of transcription factories. J. Mol. Biol. 395, 1–10. [PubMed]
de Laat, W., and Duboule, D. (2013). Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502, 499-506.
[PubMed]
Fullwood, M.J., Liu, M.H., Pan, Y.F., Liu, J., Xu, H., et al. (2009). An oestrogen-receptor-alpha-bound human chromatin interactome. Nature 462, 58-64. [PubMed]
Kolovos, P., Knoch, T.A., Grosveld, F.G., Cook, P.R., and Papantonis, A. (2012). Enhancers and silencers: an integrated and simple model for their function. Epigenetics Chromatin 5, 1. [PubMed]
Long, H.K., Prescott, S.L., and Wysocka, J. (2016). Ever-changing landscapes: transcriptional enhancers in development and evolution. Cell 167, 1170-1187. [PubMed]
Ørom, U.A., and Shiekhattar, R. (2011). Long non-coding RNAs and enhancers. Curr. Opin. Genet. Dev. 21, 194-198. [PubMed]
Osborne, C.S., Chakalova, C., Brown, K.E., Carter, D., Horton, A.,
Debrand, E., Goyenechea, B., Mitchell, J.A., Lopes, S., Reik, W. and
Fraser, P. (2004). Active genes dynamically co-localize to shared
sites of ongoing transcription. Nat. Genet. 36, 1065-1071. [PubMed]
Phillips-Cremins, J.E., and Corces, V.G. (2013). Chromatin insulators: linking genome organization to cellular function. Mol. Cell 50, 461-474.
[PubMed]
Box
6-10. Defining DNA motifs that regulate
transcription
Reference:
Marzluff, W.F. and Huang, R.C.C. (1984). Transcription of RNA in
isolated nuclei. In 'Transcription and translation: a practical
approach'. Eds B.D. Hames and S.J. Higgins. IRL Press, Oxford.
Banerji, J., Rusconi, S. and Schaffner, W. (1981). Expression of the β-globin gene is enhanced by remote SV40 DNA
sequences. Cell 27, 299-308. [PubMed]
Additional reference:
Fuda, N.J., Ardehali, M.B., and Lis, JT. (2009). Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature 461, 186-192. [PubMed]
Box. Paused polymerases [See also Box 4-4 (Transcription of heat-shock loci) in 4. Transcription.]
Reference:
Gilmour, D.S. (2009). Promoter proximal pausing on genes in metazoans. Chromosoma 118, 1-10. [PubMed]
Margaritis, T., and Holstege, F.C. (2008). Poised RNA polymerase II gives pause for thought. Cell 133, 581-514. [PubMed]
Heterochromatin
Reference:
Henikoff, S (2000). Heterochromatin function in complex genomes.
Biochim. Biophys. Acta. 1470, 1-8.
Additional reference:
Bühler, M., and Gasser, S.M. (2009). Silent chromatin at the middle and ends: lessons from yeasts. EMBO J. 28, 2149-2161. [PubMed]
Djupedal, I., and Ekwall, K. (2008). The paradox of silent heterochromatin. Science 320, 624-625. [PubMed]
Zhao, R., Bodnar, M.S., and Spector, D.L. (2009). Nuclear neighborhoods and gene expression. Curr. Opin. Genet. 19, 172-179. [PubMed]
Effects at the periphery
Towbin, B.D., Meister, P., and Gasser, S.M. (2009).
Silent chromatin at the middle and ends: lessons from yeasts.
Curr. Opin. Genet. Dev. 19, 180-186. [PubMed]
Silencing in
yeast
Figure: 6-11.
Reference:
Gottschling, D.E., Aparicio, O.M., Billington, B.L. and Zakian, V.A.
(1990). Position effect at S. cerevisiae telomeres: reversible
repression of Pol II transcription. Cell 63, 751-762. [PubMed]
Grunstein, M, (1998). Yeast heterochromatin: regulation of its assembly
and inheritance by histones. Cell 93, 325-328.
Additional reference:
Towbin, B.D., Meister, P., and Gasser, S.M. (2009). Silent chromatin at the middle and ends: lessons from yeasts. Curr. Opin. Genet. Dev. 19, 180-186. [PubMed]
DNA
methylation in vertebrates
Reference:
Bird, A.P. and Wolffe, A.P. (1999). Methylation-induced repression -
belts, braces, and chromatin. Cell 99, 451-454.
Additional reference:
Illingworth, R.S., and Bird, A.P. (2009). CpG islands--'a rough guide'. FEBS Lett. 583, 1713-1720. [PubMed]
Ooi, S.K., O'Donnell, A.H., and Bestor, T.H. (2009). Mammalian cytosine methylation at a glance. J. Cell Sci. 122, 2787-2791. [PubMed]
Polycomb
proteins of Drosophila
Reference:
Pirrotta, V. (1998). Polycombing the genome: PcG, trxG, and chromatin
silencing. Cell 93, 333-336.
Additional reference:
Simon, J.A., and Kingston, R.E. (2009). Mechanisms of polycomb gene silencing: knowns and unknowns. Nat. Rev. Mol. Cell Biol. 10, 697-708. [PubMed]
Establishing and
inheriting patterns of
expression
Additional reference:
Johnston, L.A. (2009). Competitive interactions between cells: death, growth, and geography. Science 324, 1679-1682. [PubMed]
Lawrence, P.A., and Levine, M. (2006). Mosaic and regulative
development: two faces of one coin. Curr. Biol. 16, R236-239. [PubMed]
Roellig, D., Morelli, L.G., Ares, S., Jülicher, F., and Oates, A.C. (2011). SnapShot: the segmentation clock. Cell 145, 800-800. [PubMed]
Slack, J.M. (2008). Origin of stem cells in organogenesis. Science 322, 1498-1501. [PubMed]
Web link:
http://www.ucalgary.ca/UofC/eduweb/virtualembryo/ A growing site for all things developmental.
http://genex.hgu.mrc.ac.uk/ The Edinburgh mouse atlas project.
http://www.gastrulation.org/ Movies illustrating gastrulation.
Example:
inheriting activity of rDNA genes
Figure: 6-12.
Reference:
Roussel, P., André, C., Comai, L. and Hernandez-Verdun, D.
(1996). The rDNA transcription machinery is assembled during mitosis in
active NORs and absent in inactive NORs. J. Cell Biol. 133,
235-246. [PubMed]
Chen, D., Hinkley, C.S., Henry, R.W. and Huang, S. (2002). TBP dynamics
in living human cells: constitutive association of TBP with mitotic
chromosomes. Mol. Biol. Cell 13,
276-284. [PubMed]
[Full
text]
Additional reference:
Grob, A., Colleran, C., and McStay, B. (2014). Construction of synthetic nucleoli in human cells reveals how a major functional nuclear domain is formed and propagated through cell division. Genes Dev. 28, 220-230. [PubMed]
McStay, B., and Grummt, I. (2008). The epigenetics of rRNA genes: from molecular to chromosome biology. Annu. Rev. Cell Biol. 24, 131-157. [PubMed]
Example:
anterior-posterior patterning in Drosophila eggs
Figure: 6-13.
Reference:
St. Johnston, D. and Nusslein-Volhard, C. (1992). The origin of pattern
and polarity in the Drosophila embryo. Cell 68,
201-219.
Additional reference:
Biggin, M.D. (2011). Animal transcription networks as highly connected, quantitative continua. Dev. Cell 21, 611-626. [PubMed]
De Robertis, E.M. (2006). Spemann's organizer and self-regulation
in amphibian embryos. Nat. Rev. Mol. Cell Biol. 7, 296-302. [PubMed]
Green, J.B., and Sharpe, J. (2015). Positional information and reaction-diffusion: two big ideas in developmental biology combine. Development 142, 1203-1211.
[PubMed]
Li, R. (2013). The art of choreographing asymmetric cell division. Dev. Cell 25, 439-450. [PubMed]
St. Johnston, D., and Ahringer J. (2010). Cell polarity in eggs and epithelia: parallels and diversity. Cell 141, 757-774. [PubMed]
Thompson, B.J. (2013). Cell polarity: models and mechanisms from yeast, worms and flies. Development 140, 13-21. [PubMed]
Web link:
http://www.ucalgary.ca/UofC/eduweb/virtualembryo/D_m_segment_I.html A page from the Virtual Embryo.
http://genex.hgu.mrc.ac.uk/ A
digital atlas of mouse development from Edinburgh University.
http://flymove.uni-muenster.de/Homepage.html Movies of Drosophila development from University of Muenster.
Box
6-11. Maternal-effect genes in Drosophila
Reference:
St. Johnston, D. and Nusslein-Volhard, C. (1992). The origin of pattern
and polarity in the Drosophila embryo. Cell 68,
201-219.
Additional reference:
St. Johnston, D. (2002). The art and design of genetic screens: Drosophila melanogaster. Nat. Rev. Genet. 3, 176-188. [PubMed]
Web link:
http://www.ucalgary.ca/UofC/eduweb/virtualembryo/D_m_segment_I.html A page from the Virtual Embryo.
http://flymove.uni-muenster.de/Homepage.html Movies of Drosophila development from University of Muenster.
Example:
commitment of hematopoietic stem cells
Reference:
Hu, M., Krause, D., Greaves, M., Sharkis, S., Dexter, M., Heyworth, C.
and Enver, T. (1997). Multilineage gene expression precedes commitment
in the hemopoietic system. Genes Dev. 11, 774-785. [PubMed]
Socolovsky, M., Lodish, H.F. and Daley, G.Q. (1998). Control of
hematopoietic differentiation: lack of specificity in signaling by
cytokine receptors. Proc. Natl. Acad. Sci. USA 95, 6573-6575. [Full text]
Additional reference:
Enver, T., Pera, M., Peterson, C., and Andrews, P.W. (2009). Stem cell states, fates, and the rules of attraction. Cell Stem Cell 4, 387-397. [PubMed]
Lo Celso, C., and Scadden, D.T. (2011). The haematopoietic stem cell niche at a glance. J. Cell Sci. 124, 3529-3535. [PubMed]
Tykocinski, L.O., Sinemus, A., Rezavandy, E., Weiland, Y., Baddeley, D., Cremer, C., Sonntag, S., Willecke, K., Derbinski, J., and Kyewski, B. (2010). Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells. Proc. Natl. Acad. Sci. USA 107, 19426-19431. [PubMed]
Zon, L.I. (2008). Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature 453, 306-313. [PubMed]
Example: converting fibroblasts into ES-like cells
Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676. [PubMed]
Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B.E., and Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318-324. [PubMed]
Yamanaka, S., and Blau, H. ( 2010). Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704-712. [PubMed]
Control of nuclear import and export
Additional reference:
Carmody, S.R., and Wente, S.R. (2009). mRNA nuclear export at a glance. J. Cell Sci. 122, 1933-1937. [PubMed]
Example: HIV Rev/RRE
Additional reference:
Cullen, B.R. (2003). Nuclear mRNA export: insights from virology. Trends Biochem Sci. 28, 419-424. [PubMed]
Balvay, L., Lastra, M.L., Sargueil, B., Darlix, J.L., and Ohlmann, T. (2007). Translational control of retroviruses. Nat. Rev. Microbiol. 5, 128-140. [PubMed]
Example: p53
Additional reference:
Vousden, K.H., and Prives, C. (2009). Blinded by the light: the growing complexity of p53. Cell 137, 413-31. [PubMed]
Example: Relocating a transcription factor
Cai, L., Dalal, C.K., and Elowitz, M.B. (2008). Frequency-modulated nuclear localization bursts coordinate gene regulation. Nature 455, 485-490. [PubMed]
Ashall, L., Horton, C.A., Nelson, D.E., Paszek, P., Harper, C.V. et al. (2009). Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription. Science 324, 242-246. [PubMed]
mRNA localization
Additional reference:
Buxbaum, A.R., Haimovich, G., and Singer, R.H. (2015). In the right place at the right time: visualizing and understanding mRNA localization. Nat. Rev. Mol. Cell Biol. 16, 95-109. [PubMed]
Parton, R.M., Davidson, A., Davis, I., and Weil, T.T. (2014). Subcellular mRNA localisation at a glance. J. Cell Sci. 127, 2127-2133. [PubMed]
Zip-codes
Additional reference:
Czaplinski, K., and Singer, R.H. (2006). Pathways for mRNA localization in the cytoplasm. Trends Biochem. Sci. 31, 687-693. [PubMed]
Some examples
Additional reference:
Aakalu, G. et al. (2001). Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30, 489-502. [PubMed]
Bertrand, E. et al. (1998). Localization of ASH1 mRNA particles in living yeast. Mol. Cell 2, 437-445. [PubMed]
Cha, B.J. et al. (2001). In vivo analysis of Drosophila bicoid mRNA localization reveals a novel microtubule-dependent axis specification pathway. Cell 106, 35-46. [PubMed]
Groisman, I. et al. (2000). CPEB, maskin, and cyclin B1 mRNA at the mitotic apparatus: implications for local translational control of cell division. Cell 103, 435-447. [PubMed]
Kislauskis, E.H. et al. (1993). Isoform-specific 3'-untranslated sequences sort alpha-cardiac and beta-cytoplasmic actin messenger RNAs to different cytoplasmic compartments. J. Cell Biol. 123, 165-172. [PubMed]
Zhou, Y. and King, M.L. (1996). Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes. Development 122, 2947-2953. [PubMed]
mRNA turnover
Additional reference:
Balagopal, V., and Parker, R. (2009). Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr. Opin. Cell Biol. 21, 403-408. [PubMed]
mRNA levels do not necessarily reflect the translation rate
Additional reference:
Gygi, S.P., Rochon, Y., Franza, B.R. and Aebersold, R. (1999). Correlation between protein and mRNA abundance in yeast. Mol. Cell Biol. 19, 1720-1730. [PubMed]
Beyer, A., Hollunder, J., Nasheuer, H.P. and Wilhelm, T. (2004). Post-transcriptional expression regulation in the yeast Saccharomyces cerevisiae on a genomic scale. Mol. Cell. Proteomics. 3, 1083-1092. [PubMed]
Decapping and deadenylation
Additional reference:
Gu, M., and Lima, C.D. (2005). Processing the message: structural insights into capping and decapping mRNA. Curr. Opin. Struct. Biol. 15, 99-106. [PubMed]
Parker, R., and Song, H. (2004). The enzymes and control of eukaryotic mRNA turnover. Nat. Struct. Mol. Biol. 11, 121-127. [PubMed]
Nonsense-mediated decay; does some occur in the nucleus?
Additional reference:
See 'Fidelity and quality control' in 'Chapter 4: Transcription'.
Decapping and decay occur in cytoplasmic processing bodies
Additional reference:
Balagopal, V., and Parker, R. (2009). Polysomes, P bodies and stress granules: states and fates of eukaryotic mRNAs. Curr. Opin. Cell Biol. 21, 403-408. [PubMed]
Sheth, U. and Parker, R. (2003). Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300, 805-808. [PubMed]
RNAi
See Box 6.7
Regulation at the ribosome
Additional reference:
Groppo, R., and Richter, J.D. (2009). Translational control from head to tail. Curr. Opin. Cell Biol. 21, 444-451. [PubMed]
mRNA and amino acid supply
Additional reference:
Kimball, S.R., Jefferson, L.S. (2005). Role of amino acids in the translational control of protein synthesis in mammals. Semin. Cell Dev. Biol. 16, 21-27. [PubMed]
Translation factors
Additional reference:
Sonenberg, N., and Hinnebusch, A.G. (2009). Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136, 731-745. [PubMed]
Regulatory motifs at each end of the mRNA
Additional reference:
Groppo, R., and Richter, J.D. (2009). Translational control from head to tail. Curr. Opin. Cell Biol. 21, 444-451. [PubMed]
Pantopoulos, K. (2004). Iron metabolism and the IRE/IRP regulatory system: an update. Ann. N. Y. Acad. Sci. 1012, 1-13. [PubMed]
Example: Some tricks played by viruses
Additional reference:
Firth, A.E., and Brierley, I. (2012). Non-canonical translation in RNA viruses. J. Gen. Virol. 93, 1385-1409. [PubMed]
Protein modification and turnover
Additional reference:
Cubeñas-Potts, C., and Matunis, M.J. (2013). SUMO: a multifaceted modifier of chromatin structure and function. Dev Cell 24, 1-12. [PubMed]
Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332. [PubMed]
Navon, A., and Ciechanover, A. (2009). The 26 S proteasome: from basic mechanisms to drug targeting. J. Biol. Chem. 284, 33713-33718. [PubMed]
Wang, Y., and Dasso, M. (2009). SUMOylation and deSUMOylation at a glance. J. Cell Sci. 122, 4249-4252. [PubMed]
Yen, H.C., Xu, Q., Chou, D.M., Zhao, Z., and Elledge, S.J. (2008). Global protein stability profiling in mammalian cells. Science 322, 918-923. [PubMed]
Cotranslational modification of proteins
Additional reference:
Paik, W.K., Paik, D.C., and Kim, S. (2007). Historical review: the field of protein methylation. Trends Biochem. Sci. 32, 146-152. [PubMed]
Polevoda, B. and Sherman, F. (2000). N-terminal acetylation of eukaryotic proteins. J. Biol. Chem. 275, 36479-36482. [PubMed]
Regulated protein degradation
Additional reference:
Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332. [PubMed]
Hochstrasser, M. (2009). Origin and function of ubiquitin-like proteins. Nature 458, 422-449. [PubMed]
Varshavsky, A. (2005). Regulated protein degradation. Trends Biochem. Sci. 30, 283-286. [PubMed]
Box. Inteins
Additional reference:
Vila-Perelló, M., and Muir, T.W. (2010). Biological applications of protein splicing. Cell 143, 191-200. [PubMed]
Heritable changes in protein structure - prions
See 'Box. Prions, aggresomes' in Chapter 4b, Translation.
How cells know where they are
Additional reference:
Lander, A.D. (2013). How cells know where they are. Science 339, 923-927. [PubMe