World Library  
Flag as Inappropriate
Email this Article

Histone code

Article Id: WHEBN0005462098
Reproduction Date:

Title: Histone code  
Author: World Heritage Encyclopedia
Language: English
Subject: Epigenetics, Histone, Epigenetic code, Heterochromatin, Chromatin remodeling
Collection: Epigenetics
Publisher: World Heritage Encyclopedia

Histone code

The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. Together with similar modifications such as DNA methylation it is part of the epigenetic code.[1] Histones associate with DNA to form nucleosomes, which themselves bundle to form chromatin fibers, which in turn make up the more familiar chromosome. Histones are globular proteins with a flexible N-terminus (taken to be the tail) that protrudes from the nucleosome. Many of the histone tail modifications correlate very well to chromatin structure and both histone modification state and chromatin structure correlate well to gene expression levels. The critical concept of the histone code hypothesis is that the histone modifications serve to recruit other proteins by specific recognition of the modified histone via protein domains specialized for such purposes, rather than through simply stabilizing or destabilizing the interaction between histone and the underlying DNA. These recruited proteins then act to alter chromatin structure actively or to promote transcription. For details of gene expression regulation by histone modifications see table below.


  • The Hypothesis 1
    • Modifications 1.1
  • Complexity of the histone code 2
  • See also 3
  • References 4
  • External links 5

The Hypothesis

The hypothesis is that chromatin-DNA interactions are guided by combinations of histone modifications. While it is accepted that modifications (such as methylation, acetylation, ADP-ribosylation, ubiquitination, citrullination, and phosphorylation) to histone tails alter chromatin structure, a complete understanding of the precise mechanisms by which these alterations to histone tails influence DNA-histone interactions remains elusive. However, some specific examples have been worked out in detail. For example, phosphorylation of serine residues 10 and 28 on histone H3 is a marker for chromosomal condensation. Similarly, the combination of phosphorylation of serine residue 10 and acetylation of a lysine residue 14 on histone H3 is a tell-tale sign of active transcription.


Well characterized modifications to histones include:[2]

Both lysine and arginine residues are known to be methylated. Methylated lysines are the best understood marks of the histone code, as specific methylated lysine match well with gene expression states. Methylation of lysines H3K4 and H3K36 is correlated with transcriptional activation while demethylation of H3K4 is correlated with silencing of the genomic region. Methylation of lysines H3K9 and H3K27 is correlated with transcriptional repression.[3] Particularly, H3K9me3 is highly correlated with constitutive heterochromatin.[4]

  • Acetylation — by HAT (histone acetyl transferase); deacetylation — by HDAC (histone deacetylase)

Acetylation tends to define the ‘openness’ of chromatin as acetylated histones cannot pack as well together as deacetylated histones.

However there are many more histone modifications, and sensitive mass spectrometry approaches have recently greatly expanded the catalog.[5]

A very basic summary of the histone code for gene expression status is given below (histone nomenclature is described here):

Type of
H3K4 H3K9 H3K14 H3K27 H3K79 H4K20 H2BK5
mono-methylation activation[6] activation[7] activation[7] activation[7][8] activation[7] activation[7]
di-methylation activation repression[3] repression[3] activation[8]
tri-methylation activation[9] repression[7] repression[7] activation,[8]
acetylation activation[9] activation[9]
  • H3K4me3 is found in actively transcribed promoters, particularly just after the transcription start site.
  • H3K9me3 is found in constitutively repressed genes.
  • H3K27me is found in facultatively repressed genes.[7]
  • H3K36me3 is found in actively transcribed gene bodies.
  • H3K9ac is found in actively transcribed promoters.
  • H3K14ac is found in actively transcribed promoters.

Complexity of the histone code

Unlike this simplified model, any real histone code has the potential to be massively complex; each of the four standard histones can be simultaneously modified at multiple different sites with multiple different modifications. To give an idea of this complexity, histone H3 contains nineteen lysines known to be methylated — each can be un-, mono-, di- or tri-methylated. If modifications are independent, this allows a potential 419 or 280 billion different lysine methylation patterns, far more than the maximum number of histones in a human genome (6.4 Gb / ~150 bp = ~44 million histones if they are very tightly packed). And this does not include lysine acetylation (known for H3 at nine residues), arginine methylation (known for H3 at three residues) or threonine/serine/tyrosine phosphorylation (known for H3 at eight residues), not to mention modifications of other histones.

Every nucleosome in a cell can therefore have a different set of modifications, raising the question of whether common patterns of histone modifications exist. A recent study of about 40 histone modifications across human gene promoters found over 4000 different combinations used, over 3000 occurring at only a single promoter. However, patterns were discovered including a set of 17 histone modifications that are present together at over 3000 genes.[10] Therefore, patterns of histone modifications do occur but they are very intricate, and we currently have detailed biochemical understanding of the importance of a relatively small number of modifications.

Structural determinants of histone recognition by readers, writers and erasers of the histone code are revealed by a growing body of experimental data.[11]

See also


  1. ^ Jenuwein T, Allis C (2001). "Translating the histone code". Science 293 (5532): 1074–80.  
  2. ^ Strahl B, Allis C (2000). "The language of covalent histone modifications". Nature 403 (6765): 41–5.  
  3. ^ a b c d Rosenfeld, Jeffrey A; Wang, Zhibin; Schones, Dustin; Zhao, Keji; DeSalle, Rob; Zhang, Michael Q (31 March 2009). "Determination of enriched histone modifications in non-genic portions of the human genome.". BMC Genomics 10: 143.  
  4. ^ Hublitz, Philip; Albert, Mareike; Peters, Antoine (28 April 2009). "Mechanisms of Transcriptional Repression by Histone Lysine Methylation". The International Journal of Developmental Biology (Basel) 10 (1387): 335–354.  
  5. ^ Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, et al. (2011). "Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification.". Cell 146 (6): 1016–28.  
  6. ^ Benevolenskaya EV (August 2007). "Histone H3K4 demethylases are essential in development and differentiation". Biochem. Cell Biol. 85 (4): 435–43.  
  7. ^ a b c d e f g h i Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (May 2007). "High-resolution profiling of histone methylations in the human genome". Cell 129 (4): 823–37.  
  8. ^ a b c Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR (April 2008). "DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells". Mol. Cell. Biol. 28 (8): 2825–39.  
  9. ^ a b c Koch CM, Andrews RM, Flicek P, Dillon SC, Karaöz U, Clelland GK, Wilcox S, Beare DM, Fowler JC, Couttet P, James KD, Lefebvre GC, Bruce AW, Dovey OM, Ellis PD, Dhami P, Langford CF, Weng Z, Birney E, Carter NP, Vetrie D, Dunham I (June 2007). "The landscape of histone modifications across 1% of the human genome in five human cell lines". Genome Res. 17 (6): 691–707.  
  10. ^ Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, et al. (2008). "Combinatorial patterns of histone acetylations and methylations in the human genome.". Nat Genet 40 (7): 897–903.  
  11. ^ Wang M, Mok MW, Harper H, Lee WH, Min J, Knapp S, Oppermann U, Marsden B, Schapira M (24 Aug 2010). "Structural Genomics of Histone Tail Recognition". Bioinformatics 26 (20): 2629–2630.  

External links

  • Histone Modifications with function and attached references
  • Histone Code Overview sheet
  • Histone Modification Guide
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Hawaii eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.