Key Points
-
The histone tails contain a plethora of post-translational modification (PTM) sites and are modified in various ways. One explanation for this exceptionally dense region of PTMs within chromatin is to provide a platform for signal integration and storage.
-
Histone phosphorylation seems to be a mechanism for rapid alteration of the epigenetic state. Phosphorylation can promote the binding of proteins to chromatin as well as antagonize the read-out, deposition or removal of long-lived histone tail PTMs.
-
Metabolic states may directly regulate the activity of many chromatin-modifying enzymes.
-
How activated signalling cascades control chromatin regulators is poorly understood. The best-characterized examples so far include direct regulation of the chromatin machinery through phosphorylation–dephosphorylation of enzymes and histone chaperones to tailor their activity.
-
Signal storage and output on and from chromatin may work as a biological 'digital-to-analogue' converter, integrating the on and off signals received over a time course to control the amplitude of gene transcription.
-
During critical developmental periods, an organism is more sensitive to environmental inputs. This is partially due to increased communication between activated signalling pathways and epigenetic regulators, as well as an increased ability to lay down long-lived epigenetic marks.
Abstract
Cells of a multicellular organism, all containing nearly identical genetic information, respond to differentiation cues in variable ways. In addition, cells are plastic, able to execute their specialized function while maintaining the ability to adapt to environmental changes. This is achieved through multiple mechanisms, including the direct regulation of chromatin-based processes in response to stimuli. How signal transduction pathways directly communicate with chromatin to change the epigenetic landscape is poorly understood. The preponderance of covalent modifications on histone tails coupled with a relatively small number of functional outputs raises the possibility that chromatin acts as a site of signal integration and storage.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Slattery, M. et al. Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins. Cell 147, 1270–1282 (2011).
Stark, G. & Darnell, J. The JAK–STAT pathway at twenty. Immunity 36, 503–514 (2012).
Kodadek, T., Sikder, D. & Nalley, K. Keeping transcriptional activators under control. Cell 127, 261–264 (2006).
Young, N. et al. High throughput characterization of combinatorial histone codes. Mol. Cell Proteom. 8, 2266–2284 (2009).
Strahl, B. & Allis, C. The language of covalent histone modifications. Nature 403, 41–45 (2000).
Cheung, P., Allis, C. & Sassone-Corsi, P. Signaling to chromatin through histone modifications. Cell 103, 263–271 (2000).
Greer, E. et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365–436 (2011).
Schreiber, S. & Bernstein, B. Signaling network model of chromatin. Cell 111, 771–778 (2002).
Bao, Y. Chromatin response to DNA double-strand break damage. Epigenomics 3, 307–328 (2011).
Conaway, J. W. Introduction to theme “Chromatin, epigenetics, and transcription”. Annu. Rev. Biochem. 81, 61–64 (2012).
Greer, E. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nature Rev. Genet. 13, 343–400 (2012).
Spitale, R., Tsai, M.-C. & Chang, H. RNA templating the epigenome: long noncoding RNAs as molecular scaffolds. Epigenetics 6, 539–582 (2011).
Iberg, A. et al. Arginine methylation of the histone H3 tail impedes effector binding. J. Biol. Chem. 283, 3006–3016 (2008).
Guccione, E. et al. Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive. Nature 449, 933–940 (2007). This paper was among the first to describe how methylation of one histone tail residue can directly influence the deposition and read-out of an adjacent methylation event.
Hyllus, D. et al. PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4 trimethylation. Genes Dev. 21, 3369–3449 (2007).
Eustermann, S. et al. Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin. Nature Struct. Mol. Biol. 18, 777–859 (2011).
Qiu, Y. et al. Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription. Genes Dev. 26, 1376–1467 (2012).
Suganuma, T. & Workman, J. Signals and combinatorial functions of histone modifications. Annu. Rev. Biochem. 80, 473–572 (2011).
Taverna, S., Li, H., Ruthenburg, A., Allis, C. & Patel, D. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nature Struct. Mol. Biol. 14, 1025–1065 (2007).
Ruthenburg, A. et al. Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions. Cell 145, 692–706 (2011). Describes how BPTF (bromodomain PHD finger transcription factor; which harbours multiple reader domains) can simultaneously bind two activating histone marks on different histone tails. Provided an early example of a multivalent histone tail read-out.
Alabert, C. & Groth, A. Chromatin replication and epigenome maintenance. Nature Rev. Mol. Cell Biol. 13, 153–167 (2012).
Ripperger, J. & Merrow, M. Perfect timing: epigenetic regulation of the circadian clock. FEBS Lett. 585, 1406–1411 (2011).
Zee, B., Levin, R., Dimaggio, P. & Garcia, B. Global turnover of histone post-translational modifications and variants in human cells. Epigenetics Chromatin 3, 22 (2010).
Barth, T. & Imhof, A. Fast signals and slow marks: the dynamics of histone modifications. Trends Biochem. Sci. 35, 618–644 (2010).
Banerjee, T. & Chakravarti, D. A peek into the complex realm of histone phosphorylation. Mol. Cell. Biol. 31, 4858–4931 (2011).
Baek, S. When signaling kinases meet histones and histone modifiers in the nucleus. Mol. Cell 42, 274–358 (2011).
Wei, Y., Yu, L., Bowen, J., Gorovsky, M. & Allis, C. Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97, 99–208 (1999).
Cheung, P. et al. Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol. Cell 5, 905–920 (2000).
Thomson, S., Clayton, A. & Mahadevan, L. Independent dynamic regulation of histone phosphorylation and acetylation during immediate–early gene induction. Mol. Cell 8, 1231–1272 (2001).
Vicent, G. et al. Induction of progesterone target genes requires activation of Erk and Msk kinases and phosphorylation of histone H3. Mol. Cell 24, 367–448 (2006).
Zippo, A. et al. Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation. Cell 138, 1122–1136 (2009).
Dawson, M. et al. JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin. Nature 461, 819–822 (2009).
Liokatis, S. et al. Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events. Nature Struct. Mol. Biol. 19, 819–823 (2012). Describes the hierarchy of histone tail phosphorylation events and the crosstalk with adjacent modifications.
Metzger, E. et al. Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4. Nature 464, 792–798 (2010).
Lau, P. & Cheung, P. Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing. Proc. Natl Acad. Sci. USA 108, 2801–2807 (2011).
Yang, W. et al. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 150, 685–696 (2012).
Avraham, R. & Yarden, Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nature Rev. Mol. Cell Biol. 12, 104–121 (2011).
Xiong, S., Salazar, G., Patrushev, N. & Alexander, R. FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J. Biol. Chem. 286, 5289–5388 (2011).
Latham, J., Chosed, R., Wang, S. & Dent, S. Chromatin signaling to kinetochores: transregulation of Dam1 methylation by histone H2B ubiquitination. Cell 146, 709–728 (2011). The first description of the crosstalk between marks on histones and non-histone proteins as a true 'signalling-out event.
Lu, C. & Thompson, C. Metabolic regulation of epigenetics. Cell Metab. 16, 9–17 (2012).
Melvin, A. & Rocha, S. Chromatin as an oxygen sensor and active player in the hypoxia response. Cell. Signal. 24, 35–78 (2012).
Zhou, X. et al. Hypoxia induces trimethylated H3 lysine 4 by inhibition of JARID1A demethylase. Cancer Res. 70, 4214–4235 (2010).
Chowdhury, R. et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 12, 463–469 (2011).
Lu, C. et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483, 474–478 (2012). Shows how increased levels of 2-hydroxyglutarate, resulting from mutations in isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 that are found in cancers, block demethylase activity to prevent differentiation.
Shimazu, T. et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339, 211–214 (2013).
Fujiki, R. et al. GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 459, 455–464 (2009).
Fujiki, R. et al. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480, 557–617 (2011).
Hanover, J., Krause, M. & Love, D. Bittersweet memories: linking metabolism to epigenetics through O-GlcNAcylation. Nature Rev. Mol. Cell Biol. 13, 312–333 (2012).
Kaelin, W. Jr. Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb. Symp. Quant. Biol. 76, 335–345 (2011).
Sassone-Corsi, P. Physiology. When metabolism and epigenetics converge. Science 339, 148–150 (2013).
Yang, X.-J. & Seto, E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol. Cell 31, 449–510 (2008).
Cha, T.-L. et al. Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 310, 306–310 (2005).
Nacerddine, K. et al. Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer. J. Clin. Invest. 122, 1920–1952 (2012).
Huang, W.-C. & Chen, C.-C. Akt phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity. Mol. Cell. Biol. 25, 6592–7194 (2005).
Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).
stève, P.-O. et al. A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability. Nature Struct. Mol. Biol. 18, 42–50 (2011).
Hervouet, E. et al. Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS ONE 5, e11333 (2010).
Arita, K., Ariyoshi, M., Tochio, H., Nakamura, Y. & Shirakawa, M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature 455, 818–821 (2008).
Avvakumov, G. et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455, 822–825 (2008).
Hashimoto, H. et al. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature 455, 826–829 (2008).
Hennessy, B., Smith, D., Ram, P., Lu, Y. & Mills, G. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nature Rev. Drug Discov. 4, 988–1992 (2005).
Bernstein, B. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).
Svotelis, A. et al. H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERα ligand dependency. EMBO J. 30, 3947–3961 (2011).
Creyghton, M. et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl Acad. Sci. USA 107, 21931–21936 (2010).
Visel, A. et al. ChIP–seq accurately predicts tissue-specific activity of enhancers. Nature 457, 854–858 (2009).
Hargreaves, D. & Crabtree, G. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 21, 396–420 (2011).
Forcales, S. et al. Signal-dependent incorporation of MyoD–BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. EMBO J. 31, 301–317 (2012).
Palacios, D. et al. TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration. Cell Stem Cell 7, 455–524 (2010).
Bedford, M. & Clarke, S. Protein arginine methylation in mammals: who, what, and why. Mol. Cell 33, 1–13 (2009).
Zhao, Q. et al. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nature Struct. Mol. Biol. 16, 304–315 (2009).
Liu, F. et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell 19, 283–377 (2011).
Levy, D. et al. Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling. Nature Immunol. 12, 29–65 (2011).
Day, J. & Sweatt, J. Epigenetic mechanisms in cognition. Neuron 70, 813–842 (2011).
Maze, I., Noh, K.-M. & Allis, C. Histone regulation in the CNS: basic principles of epigenetic plasticity. Neuropsychopharmacology 38, 3–22 (2012).
West, A. & Greenberg, M. Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb. Persp. Biol. 3, a005744 (2011).
Okuno, H. Regulation and function of immediate-early genes in the brain: beyond neuronal activity markers. Neurosci. Res. 69, 175–261 (2011).
Tagami, H., Ray-Gallet, D., Almouzni, G. & Nakatani, Y. Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116, 51–112 (2004).
Michod, D. et al. Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron 74, 122–157 (2012). Demonstrates that storage of a cellular experience in neurons is partly mediated through marking activity-induced genes with histone variant H3.3.
Ng, R. & Gurdon, J. Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription. Nature Cell Biol. 10, 102–111 (2008).
Su, D. et al. Structural basis for recognition of H3K56-acetylated histone H3–H4 by the chaperone Rtt106. Nature 483, 104–111 (2012).
Chang, Y. et al. MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a. Nature Commun. 2, 533 (2011).
Fischle, W., Wang, Y. & Allis, C. Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475–484 (2003).
Nicodeme, E. et al. Suppression of inflammation by a synthetic histone mimic. Nature 468, 1119–1123 (2010). This clinically important paper shows that a histone-mimic compound (I-BET) that binds the acetylated Lys residues in the binding pocket of BRD2, BRD3 and BRD4 can prevent inflammation-induced gene expression in vitro and in vivo.
Marazzi, I. et al. Suppression of the antiviral response by an influenza histone mimic. Nature 483, 428–433 (2012).
Chin, H. et al. Automethylation of G9a and its implication in wider substrate specificity and HP1 binding. Nucleic Acids Res. 35, 7313–7336 (2007).
Sampath, S. et al. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol. Cell 27, 596–1204 (2007).
Tachibana, M. et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3–K9. Genes Dev. 19, 815–826 (2005).
Kim, H. et al. p53 requires an intact C-terminal domain for DNA binding and transactivation. J. Mol. Biol. 415, 843–897 (2012).
Huang, J. et al. p53 is regulated by the lysine demethylase LSD1. Nature 449, 105–113 (2007).
Chuikov, S. et al. Regulation of p53 activity through lysine methylation. Nature 432, 353–413 (2004).
West, L. & Gozani, O. Regulation of p53 function by lysine methylation. Epigenomics 3, 361–370 (2011).
Kruse, J.-P. & Gu, W. Modes of p53 regulation. Cell 137, 609–631 (2009).
Cui, G. et al. PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53. Nature Struct. Mol. Biol. 19, 916–924 (2012).
Badeaux, A. et al. Loss of the methyl lysine effector protein PHF20 impacts the expression of genes regulated by the lysine acetyltransferase MOF. J. Biol. Chem. 287, 429–466 (2012).
Park, S. et al. Identification of Akt interaction protein PHF20/TZP that transcriptionally regulates p53. J. Biol. Chem. 287, 11151–11214 (2012).
Brookes, E. & Pombo, A. Modifications of RNA polymerase II are pivotal in regulating gene expression states. EMBO Rep. 10, 1213–1219 (2009).
Levine, M. Paused RNA polymerase II as a developmental checkpoint. Cell 145, 502–513 (2011).
Hsin, J.-P., Sheth, A. & Manley, J. RNAP II CTD phosphorylated on threonine-4 is required for histone mRNA 3′ end processing. Science 334, 683–689 (2011).
Mayer, A. et al. CTD tyrosine phosphorylation impairs termination factor recruitment to RNA polymerase II. Science 336, 1723–1728 (2012).
Ranuncolo, S., Ghosh, S., Hanover, J., Hart, G. & Lewis, B. Evidence of the involvement of O-GlcNAc-modified human RNA polymerase II CTD in transcription in vitro and in vivo. J. Biol. Chem. 287, 23549–23561 (2012).
Sims, R. et al. The C-terminal domain of RNA polymerase II is modified by site-specific methylation. Science 332, 99–202 (2011).
Yang, Y. et al. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol. Cell 40, 1016–1023 (2010).
Canani, R. et al. Epigenetic mechanisms elicited by nutrition in early life. Nutr. Res. Rev. 24, 198–403 (2011).
Symonds, M., Sebert, S., Hyatt, M. & Budge, H. Nutritional programming of the metabolic syndrome. Nature Rev. Endocrinol. 5, 604–614 (2009).
Walker, C. & Ho, S.-M. Developmental reprogramming of cancer susceptibility. Nature Rev. Cancer 12, 479–565 (2012).
Trollope, A. et al. Stress, epigenetic control of gene expression and memory formation. Exp. Neurol. 233, 3–14 (2012).
Zovkic, I. & Sweatt, J. Epigenetic mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology 38, 77–93 (2012).
Kantojärvi, K. et al. Analysis of 9p24 and 11p12-13 regions in autism spectrum disorders: rs1340513 in the JMJD2C gene is associated with ASDs in Finnish sample. Psychiatr. Genet. 20, 102–108 (2010).
Wang, K.-S., Liu, X., Zhang, Q., Wu, L.-Y. & Zeng, M. Genome-wide association study identifies 5q21 and 9p24.1 (KDM4C) loci associated with alcohol withdrawal symptoms. J. Neural Transm. 119, 425–433 (2012).
Iwase, S. et al. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128, 1077–1088 (2007).
Ounap, K. et al. A novel c.2T > C mutation of the KDM5C/JARID1C gene in one large family with X-linked intellectual disability. Eur. J. Med. Genet. 55, 178–184 (2012).
Kleefstra, T. et al. Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. Am. J. Hum. Genet. 91, 73–82 (2012).
O'Roak, B. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246–250 (2012).
Laumonnier, F. et al. Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J. Med. Genet. 42, 780–786 (2005).
Ong, C.-T. & Corces, V. Enhancer function: new insights into the regulation of tissue-specific gene expression. Nature Rev. Genet. 12, 283–293 (2011).
Boeke, J. et al. Phosphorylation of SU(VAR)3-9 by the chromosomal kinase JIL-1. PLoS ONE 5, e10042 (2010).
Chi, Y. et al. Identification of CDK2 substrates in human cell lysates. Genome Biol. 9, R149 (2008).
Liu, H. et al. Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint. Nature 467, 343–346 (2010).
Wu, S. et al. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev. 24, 2531–2542 (2010).
Spektor, T., Congdon, L., Veerappan, C. & Rice, J. The UBC9 E2 SUMO conjugating enzyme binds the PR-Set7 histone methyltransferase to facilitate target gene repression. PLoS ONE 6, e22785 (2011).
Chen, S. et al. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nature Cell Biol. 12, 1108–1122 (2010).
Wei, Y. et al. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nature Cell Biol. 13, 87–181 (2011).
Baba, A. et al. PKA-dependent regulation of the histone lysine demethylase complex PHF2–ARID5B. Nature Cell Biol. 13, 668–743 (2011).
Liu, W. et al. PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature 466, 508–512 (2010).
Feng, Q. et al. Biochemical control of CARM1 enzymatic activity by phosphorylation. J. Biol. Chem. 284, 36167–36241 (2009).
Higashimoto, K., Kuhn, P., Desai, D., Cheng, X. & Xu, W. Phosphorylation-mediated inactivation of coactivator-associated arginine methyltransferase 1. Proc. Natl Acad. Sci. USA 104, 12318–12323 (2007).
Estève P. O. et al. Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells. Proc. Natl Acad. Sci. USA 106, 5076–5081 (2009)
Lee, B. & Muller M. T. SUMOylation enhances DNA methyltransferase 1 activity. Biochem. J. 421, 449–461 (2009)
Sugiyama Y. et al. The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1δ/ɛ. Biochem J. 427, 489–497 (2010)
Lavoie G. & St-Pierre Y. Phosphorylation of human DNMT1: implication of cyclin-dependent kinases. Biochem. Biophys. Res. Commun. 409, 187–192 (2011)
Bourachot, B., Yaniv, M. & Muchardt, C. Growth inhibition by the mammalian SWI-SNF subunit Brm is regulated by acetylation. EMBO J. 22, 6505–6515 (2003).
Galisson, F. et al. A novel proteomics approach to identify SUMOylated proteins and their modification sites in human cells. Mol Cell Proteomics 10, M110.004796 (2011).
Hsiao, H.-H., Meulmeester, E., Frank, B., Melchior, F. & Urlaub, H. “ChopNSpice, ” a mass spectrometric approach that allows identification of endogenous small ubiquitin-like modifier-conjugated peptides. Mol. Cell Proteom. 8, 2664–2675 (2009).
Acknowledgements
The authors thank E. Brookes and E. Greer for critical reading of the manuscript. A.I.B. is supported by the Developmental Neurology Institutional National Research Service Award (NRSA), Training Grant, T32 NS007473. Research in the Shi lab is supported by grants from the NIH (CA118478, MH096066, GM058012 and GM071044) and the Ellison Medical Foundation. Y. Shi is an American Cancer Society Research Professor. The authors apologize to colleagues whose work could not be cited owing to space limitations.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Related links
Glossary
- Writer
-
Enzyme with the ability to add chemical modifications to DNA or histones.
- Eraser
-
Enzyme with the ability to remove chemical modifications from DNA or histones.
- Reader
-
A protein that binds histones or DNA only when certain chemical modifications are present (or absent). They often contain similar protein domains for recognizing similar modifications; for example, many chromodomain containing proteins bind to di- or trimethylated Lys 9 on histone H3.
- Histone variants
-
Multiple genes encode for each histone family (H1, H3, H4, H2A and H2B), resulting in family members with slight sequence variation (for example, H3.1 and H3.3). The subtle differences between family members can lead to different functional outcomes once incorporated into nucleosomes, and therefore histone variant utilization offers another level of control for transcription, replication and DNA repair.
- Nucleosome remodellers
-
ATP-dependent enzymes that catalyse a shift in the nucleosome position relative to the DNA sequence. The various families of remodellers use slightly different mechanisms to facilitate nucleosome repositioning.
- Histone chaperones
-
Proteins that associate with histones to facilitate a number of functions, including histone transfer, deposition into or eviction from chromatin, histone variant utilization and storage.
- Bivalent domains
-
Chromatin regions that harbour 'active' and 'repressive' histone modifications. Bivalent domains are thought to mark genes that are expressed at low levels only, but that are poised for activation upon a differentiation cue or other signalling events.
- Primary response genes
-
(PRGs). A gene class that is rapidly induced upon cellular stimulation. Transcription of this gene class occurs independently of new protein production, via proteins that are already present in the cell nucleus.
Rights and permissions
About this article
Cite this article
Badeaux, A., Shi, Y. Emerging roles for chromatin as a signal integration and storage platform. Nat Rev Mol Cell Biol 14, 211–224 (2013). https://doi.org/10.1038/nrm3545
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrm3545
This article is cited by
-
TRIM3 facilitates ferroptosis in non-small cell lung cancer through promoting SLC7A11/xCT K11-linked ubiquitination and degradation
Cell Death & Differentiation (2024)
-
High Temperature Triggers Differential Expression of JUMONJI C (JmjC) Domain-Containing Histone Demethylase Genes in Leaf and Stolon Tissues of Potato (Solanum tuberosum L.) Genotypes
Journal of Plant Growth Regulation (2023)
-
Histone Modifying Potential of Dietary Phytochemicals: Implications in Treating Breast Cancer
Current Pharmacology Reports (2023)
-
Neuroinflammation regulates the balance between hippocampal neuron death and neurogenesis in an ex vivo model of thiamine deficiency
Journal of Neuroinflammation (2022)
-
Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in Jatropha curcas L.
Scientific Reports (2022)
