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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).


Histone Modifications Products

   Histone and histone modification antibodies

   Histone modifying enzymes

   Histone modification ELISAs

   Histone purification kits


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


   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.