Histone modifications associated with somatic hypermutation

Immunity. 2005 Jul;23(1):101-10. doi: 10.1016/j.immuni.2005.05.007.

Abstract

A number of modified histones, including acetylated H3 and H4 and phosphorylated H2AX (gammaH2AX), are associated with V(D)J recombination and class switch recombination (CSR). In contrast, little is known concerning the chromatin modifications associated with somatic hypermutation (SHM) in vivo. Here, we report that several modifications--including histone acetylation and H3-lysine 4 methylation--fail to demarcate an actively hypermutating immunoglobulin (Ig) locus or to correlate spatially with SHM within Ig loci. Furthermore, no obvious association between SHM and gammaH2AX could be detected. Instead, we find that the phosphorylated form of histone H2B (H2B(Ser14P)) correlates tightly with SHM and CSR. Phosphorylation of H2B within Ig variable and switch regions requires AID and may be mediated by the histone kinase Mst1. These findings indicate that SHM and CSR trigger distinct DNA damage responses and identify a novel histone modification pattern for SHM consisting of H2B(Ser14P) in the absence of gammaH2AX.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • B-Lymphocytes / metabolism*
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • CpG Islands
  • DNA Damage
  • DNA Methylation
  • Histones / genetics
  • Histones / metabolism*
  • Immunoglobulin Class Switching*
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / metabolism
  • Immunoglobulin lambda-Chains / genetics
  • Immunoglobulin lambda-Chains / metabolism
  • Methylation
  • Mice
  • Mice, Transgenic
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / physiology
  • Somatic Hypermutation, Immunoglobulin*

Substances

  • Chromatin
  • Histones
  • Immunoglobulin Light Chains
  • Immunoglobulin lambda-Chains
  • gamma-H2AX protein, mouse
  • Stk4 protein, mouse
  • Protein-Serine-Threonine Kinases