Histone Modifications Guide

Information regarding histone modifications, their biological relevance and the proteins involved in their regulation.

The three billion base pairs of DNA in each of your cells are incorporated into chromatin by associating with a group of small evolutionarily conserved proteins, the histones. Two molecules each of the core histone proteins (H2A, H2B, H3 and H4) form an octamer where ~147 bp of DNA wraps around it to create the fundamental repeating subunit of chromatin, the nucleosome. A specialized histone (linker histone H1) functions to further compact the tens of millions of nucleosomes into more highly ordered structures. It is this compacted DNA-protein complex that serves as the template for all DNA-dependent processes including DNA replication, repair, recombination, chromo­some segregation and gene expression.

It has long been known that the histones are subject to a variety of post-translational modifications (phosphorylation, acetylation, ubiquitylation, methylation: two different types – arginine and lysine) and that these modifications play important roles in chromatin structure and function. With regard to transcriptional regulation, increases in histone acetylation and specific methylation events (H3 lysine 4 & lysine 36 methylation) are generally associated with increased gene expression, while decreased acetylation and other histone methylation events (H3 lysine 9 and lysine 27 methylation) are hallmarks of decreased gene expression (See reference 6 for a recent review).

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Histone Modifications Map

Histone Modifications.

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Histone Modifications and Associated Biological Function

Histone H2A
Site Modification Associated Function
Ser1 Phosphorylation Mitosis
Lys5 Acetylation Transcriptional activation
Lys119 Ubiquitylation Spermatogenesis
Thr120 Phosphorylation Mitosis

 

Histone H2AX
Site Modification Associated Function
Ser139 Phosphorylation DNA Damage repair, apoptosis
Tyr142 Phosphorylation Regulation of DNA damage foci formation

 

Histone H2B
Site Modification Associated Function
Lys5 Acetylation Transcriptional activation
Lys12 Acetylation Transcriptional activation
Ser14 Phosphorylation Apoptosis
Lys15 Acetylation Transcriptional activation
Lys20 Acetylation Transcriptional activation
Lys120 Ubiquitylation Transcription (elongation?)

 

Histone H3
Site Modification Associated Function
Arg2 Methylation Transcriptional activation
Thr3 Phosphorylation Mitosis
Lys4 Acetylation Transcriptional activation
Lys4 Methylation Euchromatin, transcriptional activation
Thr6 Phosphorylation Transcriptional activation
Arg8 Methylation Transcriptional activation
Lys9 Acetylation Histone deposition, Transcriptional activation
Lys9 Methylation Transcriptional silencing, heterochromatin
Ser10 Phosphorylation Mitosis, immediate early gene activation
Thr11 Phosphorylation Mitosis; DNA damage induced transcription
Lys14 Acetylation Transcriptional activation
Arg17 Methylation Transcriptional activation
Lys18 Acetylation Transcriptional activation
Lys23 Acetylation Transcriptional activation
Arg26 Methylation Transcriptional activation
Lys27 Methylation Transcriptional silencing
Ser28 Phosphorylation Mitosis
Lys36 Acetylation Transcription activation
Lys36 Methylation Transcription elongation
Thr45 Phosphorylation DNA replication, apoptosis
Lys56 Acetylation DNA damage repair, chromatin assembly
Lys79 Methylation Transcriptional activation

 

Histone H4
Site Modification Associated Function
Ser1 Phosphorylation Transcriptional activation
Arg3 Methylation Transcriptional activation
Lys5 Acetylation Histone deposition, Transcriptional activation
Lys8 Acetylation Transcriptional activation
Lys12 Acetylation Histone deposition, Transcriptional activation
Lys16 Acetylation Transcriptional activation
Lys20 Methylation Transcriptional silencing, heterochromatin
Lys91 Acetylation Histone deposition, DNA damage repair

 

References
   1. Fraga, M.F. et al. (2005) Nat. Genet. 37: 391-400.
   2. Gronbaek, K. et al. (2007) APMIS 115: 1039-1059.
   3. Jenuwein, T. (2006) FEBS J. 273: 3121-3135.
   4. Jones, P.A. (2007) Cell 128: 683-692.
   5. Kurdistani, S. (2007) Br. J. Cancer 97: 1-5.
   6. Kouzarides, T. (2007) Cell 128: 693-705.
   7. Laird, P. (2005) Hum. Mol. Genet. 2005 14, S1: R65-R76.
   8. Seligson, D.B. (2005) Nature 435: 1262-1266.
   9. Varambally, S. (2002) Nature 419: 624-629.
   10. Yu, J. (2007) Cancer Res. 2007 67: 10657-10663.