histone code


Summary: The specific patterns of changes made to HISTONES, that are involved in assembly, maintenance, and alteration of chromatin structural states (such as EUCHROMATIN and HETEROCHROMATIN). The changes are made by various HISTONE MODIFICATION PROCESSES that include ACETYLATION; METHYLATION; PHOSPHORYLATION; and UBIQUITINATION.

Top Publications

  1. Peterson C, Laniel M. Histones and histone modifications. Curr Biol. 2004;14:R546-51 pubmed
  2. Li G. Decoding the histone code: Role of H3K36me3 in mismatch repair and implications for cancer susceptibility and therapy. Cancer Res. 2013;73:6379-83 pubmed publisher
    ..In this review, potential roles for this histone mark to modulate genome stability and cancer susceptibility in human cells are discussed. ..
  3. Sakabe K, Wang Z, Hart G. Beta-N-acetylglucosamine (O-GlcNAc) is part of the histone code. Proc Natl Acad Sci U S A. 2010;107:19915-20 pubmed publisher
    ..Finally, we show that histone O-GlcNAcylation changes during mitosis and with heat shock. Taken together, these data show that O-GlcNAc cycles dynamically on histones and can be considered part of the histone code.
  4. Young N, DiMaggio P, Garcia B. The significance, development and progress of high-throughput combinatorial histone code analysis. Cell Mol Life Sci. 2010;67:3983-4000 pubmed publisher
    ..This code, the combinatorial histone code, functions much like a bar code or combination lock providing the potential for massive information content...
  5. Liu C, Lu F, Cui X, Cao X. Histone methylation in higher plants. Annu Rev Plant Biol. 2010;61:395-420 pubmed publisher
    ..The aim of this review is to summarize the biochemical, genetic, and molecular action of histone methylation in two plants, the dicot Arabidopsis and the monocot rice. ..
  6. Zippo A, Serafini R, Rocchigiani M, Pennacchini S, Krepelova A, Oliviero S. Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation. Cell. 2009;138:1122-36 pubmed publisher
    ..Thus, the single phosphorylation H3S10ph at the FOSL1 enhancer triggers a cascade of events which activate transcriptional elongation. ..
  7. Gopalakrishnan S, Sullivan B, Trazzi S, Della Valle G, Robertson K. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009;18:3178-93 pubmed publisher
    ..and DNMT3B to both centromeric and pericentromeric satellite repeats and that CENP-C and DNMT3B regulate the histone code in these regions, including marks characteristic of centromeric chromatin...
  8. Fillingham J, Greenblatt J. A histone code for chromatin assembly. Cell. 2008;134:206-8 pubmed publisher
    ..Chen et al. (2008) establish that the acetylation mark promotes chromatin reassembly following DNA double-strand break repair. ..
  9. Sims J, Rice J. PR-Set7 establishes a repressive trans-tail histone code that regulates differentiation. Mol Cell Biol. 2008;28:4459-68 pubmed publisher
    ..We previously discovered a novel trans-tail histone code involving monomethylated histone H4 lysine 20 (H4K20) and H3 lysine 9 (H3K9); however, the mechanisms that ..

More Information


  1. Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar S. Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem. 2008;283:13611-26 pubmed publisher
    ..We conclude that epigenetic mechanisms consisting of histone code modifications repress skeletal muscle glut4 transcription in the postnatal period and persist in the adult ..
  2. Escargueil A, Soares D, Salvador M, Larsen A, Henriques J. What histone code for DNA repair?. Mutat Res. 2008;658:259-70 pubmed publisher
    ..are relatively well characterized and are thought to be the result of a code on the histone proteins (histone code)...
  3. Gamble M, Kraus W. Visualizing the histone code on LSD1. Cell. 2007;128:433-4 pubmed
  4. Winter S, Simboeck E, Fischle W, Zupkovitz G, Dohnal I, Mechtler K, et al. 14-3-3 proteins recognize a histone code at histone H3 and are required for transcriptional activation. EMBO J. 2008;27:88-99 pubmed
    ..Finally, siRNA-mediated loss of 14-3-3 proteins abolishes the transcriptional activation of HDAC1. Together our data indicate that 14-3-3 proteins are crucial mediators of histone phosphoacetylation signals. ..
  5. Lai W, Buck M. An integrative approach to understanding the combinatorial histone code at functional elements. Bioinformatics. 2013;29:2231-7 pubmed publisher
    ..mjbuck@buffalo.edu ?Supplementary data are available at Bioinformatics online. ..
  6. Tropberger P, Pott S, Keller C, Kamieniarz Gdula K, Caron M, Richter F, et al. Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer. Cell. 2013;152:859-72 pubmed publisher
    ..Collectively, this suggests that transcriptional regulators elicit their effects not only via signaling to histone tails but also via direct structural perturbation of nucleosomes by directing acetylation to their lateral surface. ..
  7. Teng L, Tan K. Finding combinatorial histone code by semi-supervised biclustering. BMC Genomics. 2012;13:301 pubmed publisher
    ..SS-CoSBI is implemented in C. The source code is freely available at http://www.healthcare.uiowa.edu/labs/tan/SS-CoSBI.gz. ..
  8. Lee H, Cho H, Lee D, Kim K, Han H, Kim I. Tissue-specific upregulation of angiotensin-converting enzyme 1 in spontaneously hypertensive rats through histone code modifications. Hypertension. 2012;59:621-6 pubmed publisher
    ..In conclusion, ACE1 is upregulated in local tissues of SHRs via histone code modifications.
  9. Tan M, Luo H, Lee S, Jin F, Yang J, Montellier E, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146:1016-28 pubmed publisher
    ..These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells. ..
  10. Zhang Z, Zhang M. Histone modification profiles are predictive for tissue/cell-type specific expression of both protein-coding and microRNA genes. BMC Bioinformatics. 2011;12:155 pubmed publisher
    ..We have begun to understand the HMV patterns that guide gene expression in both tissue/cell-type specific and ubiquitous manner. ..
  11. Hottiger M. ADP-ribosylation of histones by ARTD1: an additional module of the histone code?. FEBS Lett. 2011;585:1595-9 pubmed publisher
    ..The ADP-ribose modification is read by zinc finger motifs or macrodomains, which then regulate chromatin structure and transcription. Thus, histone ADP-ribosylation may be considered an additional component of the histone code.
  12. Bronner C. Control of DNMT1 abundance in epigenetic inheritance by acetylation, ubiquitylation, and the histone code. Sci Signal. 2011;4:pe3 pubmed publisher
    ..In the case of DNMT1, the balance of UHRF1 and HAUSP activities might be influenced by the local environment, such as histone code, cell-cycle status, and local DNA methylation status.
  13. Vermeulen M, Eberl H, Matarese F, Marks H, Denissov S, Butter F, et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell. 2010;142:967-80 pubmed publisher
    ..Our data reveal a highly adapted interplay between chromatin marks and their associated protein complexes. Reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression. ..
  14. Lee J, Smith E, Shilatifard A. The language of histone crosstalk. Cell. 2010;142:682-5 pubmed publisher
    ..However, recent studies indicate that histone modifications have context-dependent effects, making their interplay more like a language within the chromatin signaling pathway than a code. ..
  15. Plazas Mayorca M, Bloom J, Zeissler U, LeRoy G, Young N, DiMaggio P, et al. Quantitative proteomics reveals direct and indirect alterations in the histone code following methyltransferase knockdown. Mol Biosyst. 2010;6:1719-29 pubmed publisher
    ..Our results provide new insights into the intra- and inter- histone cross-regulation of histone K9 methylation and its potential downstream gene targets. ..
  16. Ivanovska I, Khandan T, Ito T, Orr Weaver T. A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes. Genes Dev. 2005;19:2571-82 pubmed
    ..We analyzed the role of Histone H2A phosphorylation with respect to the histone code hypothesis and found that it is required for acetylation of Histone H3 and Histone H4 in meiosis...
  17. Morris K. siRNA-mediated transcriptional gene silencing: the potential mechanism and a possible role in the histone code. Cell Mol Life Sci. 2005;62:3057-66 pubmed
    ..e. directed control of gene expression) and biologically in understanding the evolution of the cell. ..
  18. Young N, DiMaggio P, Plazas Mayorca M, Baliban R, Floudas C, Garcia B. High throughput characterization of combinatorial histone codes. Mol Cell Proteomics. 2009;8:2266-84 pubmed publisher
    ..will be essential for determining how histone modifications occur and act in combination to propagate the histone code during transcriptional events and could greatly enable sequencing of the histone component of human epigenomes.
  19. Lomberk G, Bensi D, Fernandez Zapico M, Urrutia R. Evidence for the existence of an HP1-mediated subcode within the histone code. Nat Cell Biol. 2006;8:407-15 pubmed
    ..proteins to post-translationally modified histones is switched on and off will further our knowledge of how the histone code is modulated...
  20. Schones D, Zhao K. Genome-wide approaches to studying chromatin modifications. Nat Rev Genet. 2008;9:179-91 pubmed publisher
    ..Here we review genome-wide approaches to studying epigenomic structure and the exciting findings that have been obtained using these technologies. ..
  21. Dekker J. GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p. Genome Biol. 2007;8:R116 pubmed
    ..Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood...
  22. Garske A, Craciun G, Denu J. A combinatorial H4 tail library for exploring the histone code. Biochemistry. 2008;47:8094-102 pubmed publisher
    ..on the first 21 residues of histone H4 was designed for systematic examination of proteins that interpret a histone code. The 800-member library represented all permutations of most known modifications within the N-terminal tail of ..
  23. Boussouar F, Rousseaux S, Khochbin S. A new insight into male genome reprogramming by histone variants and histone code. Cell Cycle. 2008;7:3499-502 pubmed
    ..Here we highlight the general traits of this unconventional male-specific epigenetic code, which largely relies on the use of histone variants and specific histone modifications. ..
  24. Tjeertes J, Miller K, Jackson S. Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J. 2009;28:1878-89 pubmed publisher
    ..Collectively, our data indicate that though most histone modifications do not change appreciably after genotoxic stress, H3K9Ac and H3K56Ac are reduced in response to DNA damage in human cells. ..
  25. Corpet A, Almouzni G. A histone code for the DNA damage response in mammalian cells?. EMBO J. 2009;28:1828-30 pubmed publisher
  26. Ram O, Goren A, Amit I, Shoresh N, Yosef N, Ernst J, et al. Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell. 2011;147:1628-39 pubmed publisher
    ..Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function...
  27. Loyola A, Almouzni G. Bromodomains in living cells participate in deciphering the histone code. Trends Cell Biol. 2004;14:279-81 pubmed
  28. Suter M, Takahashi D, Grove K, Aagaard K. Postweaning exposure to a high-fat diet is associated with alterations to the hepatic histone code in Japanese macaques. Pediatr Res. 2013;74:252-8 pubmed publisher
    ..Npas2, is altered in fetal life with maternal high-fat (HF) diet exposure by virtue of alterations in the fetal histone code. We postulated that these disruptions would persist postnatally. ..
  29. Godde J, Ura K. Cracking the enigmatic linker histone code. J Biochem. 2008;143:287-93 pubmed publisher
    Recently, the existence of a 'histone code' has been proposed to explain the link between the covalent chemical modification of histone proteins and the epigenetic regulation of gene activity...
  30. Koshibu K, Graff J, Beullens M, Heitz F, Berchtold D, Russig H, et al. Protein phosphatase 1 regulates the histone code for long-term memory. J Neurosci. 2009;29:13079-89 pubmed publisher
    ..Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1. ..
  31. INIGUEZ LLUHI J. For a healthy histone code, a little SUMO in the tail keeps the acetyl away. ACS Chem Biol. 2006;1:204-6 pubmed
    ..A recent report provides exciting new evidence that conjugation of the ubiquitin-like protein SUMO to histones opposes acetylation and establishes SUMOylation as an important histone mark linked to transcriptional repression. ..
  32. Vu T, Li T, Hoffman A. Promoter-restricted histone code, not the differentially methylated DNA regions or antisense transcripts, marks the imprinting status of IGF2R in human and mouse. Hum Mol Genet. 2004;13:2233-45 pubmed
    ..We discuss these findings in light of recent progress in identifying specific components of the epigenetic marks in imprinted genes. ..
  33. Santos Rosa H, Caldas C. Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer. 2005;41:2381-402 pubmed
  34. Balakrishnan L, Milavetz B. Decoding the histone H4 lysine 20 methylation mark. Crit Rev Biochem Mol Biol. 2010;45:440-52 pubmed publisher
    ..other histone modifications associated with different biological processes in the context of a combinatorial histone code. It seems likely that continued study of the methylation of H4K20 will yield extremely valuable insights ..
  35. Prabakaran S, Lippens G, Steen H, Gunawardena J. Post-translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding. Wiley Interdiscip Rev Syst Biol Med. 2012;4:565-83 pubmed publisher
    ..We focus particularly on examples other than the well-known 'histone code', to emphasize the pervasive use of information encoding in molecular biology...
  36. Lemaire K, Granvik M, Schraenen A, Goyvaerts L, Van Lommel L, Gómez Ruiz A, et al. How stable is repression of disallowed genes in pancreatic islets in response to metabolic stress?. PLoS ONE. 2017;12:e0181651 pubmed publisher
    ..In conclusion, we show that the disallowed status of islet genes is stable under physiological challenging conditions (advanced age, pregnancy, high fat diet) but partially lost in islets from diabetic animals. ..
  37. Turner A, Margolis D. Chromatin Regulation and the Histone Code in HIV Latency?. Yale J Biol Med. 2017;90:229-243 pubmed
    ..Here we discuss recent advances in the field of chromatin regulation, specifically in our understanding of the histone code, and how these discoveries relate to our current knowledge of the chromatin mechanisms linked to HIV ..
  38. Jimenez Pacheco A, Franco J, Lopez S, Gómez Zumaquero J, Magdalena Leal Lasarte M, Caballero Hernandez D, et al. Epigenetic Mechanisms of Gene Regulation in Amyotrophic Lateral Sclerosis. Adv Exp Med Biol. 2017;978:255-275 pubmed publisher
  39. Reynard L, Turner J. Increased sex chromosome expression and epigenetic abnormalities in spermatids from male mice with Y chromosome deletions. J Cell Sci. 2009;122:4239-48 pubmed publisher
    ..This increase in transcription is accompanied by specific changes in the sex chromosome histone code, including almost complete loss of H4K8Ac and reduction of H3K9me3 and CBX1...
  40. Egloff S, Murphy S. Cracking the RNA polymerase II CTD code. Trends Genet. 2008;24:280-8 pubmed publisher
    ..How and when is the code written and read? How does it contribute to transcription and coordinate RNA processing? ..
  41. Sullivan W, Naguleswaran A, Angel S. Histones and histone modifications in protozoan parasites. Cell Microbiol. 2006;8:1850-61 pubmed
    ..As we describe in this review, such studies provide a unique vantage point of the evolutionary picture of eukaryotic cell development, and reveal unique phenomena that could be exploited pharmacologically to treat protozoal diseases. ..
  42. Woo Y, Li W. Evolutionary conservation of histone modifications in mammals. Mol Biol Evol. 2012;29:1757-67 pubmed publisher
    ..In summary, the results of this study support the view that in mammalian genomes a common mechanism maintains histone modifications against both genetic and environmental (cellular) changes. ..
  43. Haun W, Springer N. Maternal and paternal alleles exhibit differential histone methylation and acetylation at maize imprinted genes. Plant J. 2008;56:903-12 pubmed publisher
    ..This study presents a detailed view of the chromatin modifications that are associated with the maternal and paternal alleles at imprinted loci and provides evidence for common histone modifications at multiple imprinted loci. ..
  44. Kratz A, Arner E, Saito R, Kubosaki A, Kawai J, Suzuki H, et al. Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns. BMC Genomics. 2010;11:257 pubmed publisher
    ..Experimental data from DeepCAGE and ChIP-chip experiments using undifferentiated (monocyte) and differentiated (macrophage) THP-1 cells leads us to the same conclusions. ..
  45. Pham H, Ferrari R, Cokus S, Kurdistani S, Pellegrini M. Modeling the regulatory network of histone acetylation in Saccharomyces cerevisiae. Mol Syst Biol. 2007;3:153 pubmed
    ..We validate the model, both computationally and experimentally, to demonstrate that it yields accurate predictions of these regulatory mechanisms. ..
  46. Gao C, Herold J, Kireev D. Assessment of free energy predictors for ligand binding to a methyllysine histone code reader. J Comput Chem. 2012;33:659-65 pubmed publisher
    Methyllysine histone code readers constitute a new promising group of potential drug targets...
  47. Ruthenburg A, Li H, Patel D, Allis C. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007;8:983-94 pubmed
    ..We propose that multivalent interactions on a single histone tail and beyond may have a significant, if not dominant, role in chromatin transactions. ..
  48. Bernt K, Armstrong S. A role for DOT1L in MLL-rearranged leukemias. Epigenomics. 2011;3:667-70 pubmed publisher
  49. Fischle W, Schwarzer D. Probing Chromatin-modifying Enzymes with Chemical Tools. ACS Chem Biol. 2016;11:689-705 pubmed publisher
  50. Moazed D. Mechanisms for the inheritance of chromatin states. Cell. 2011;146:510-8 pubmed publisher
  51. Guillaumet Adkins A, Heyn H. Single-Cell Genomics Unravels Brain Cell-Type Complexity. Adv Exp Med Biol. 2017;978:393-407 pubmed publisher
  52. Giannopoulou E, Elemento O. An integrated ChIP-seq analysis platform with customizable workflows. BMC Bioinformatics. 2011;12:277 pubmed publisher
    ..The framework is freely available as a user-friendly GUI application, but all programs are also executable from the command line, thus providing flexibility and automatability for advanced users. ..
  53. López Rodríguez M, Kaminska D, Lappalainen K, Pihlajamaki J, Kaikkonen M, Laakso M. Identification and characterization of a FOXA2-regulated transcriptional enhancer at a type 2 diabetes intronic locus that controls GCKR expression in liver cells. Genome Med. 2017;9:63 pubmed publisher
    ..Differential haplotype regulation suggests the existence of cis regulatory effects that may contribute to the associated traits at this locus. ..