Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement

Nat Immunol. 2003 Feb;4(2):124-31. doi: 10.1038/ni876. Epub 2002 Dec 23.

Abstract

Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic development in mice, but its role in the adult organism is unknown. High expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a critical role for Ezh2 in early B cell development and rearrangement of the immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Histones / metabolism*
  • Methylation
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Milk Proteins*
  • Mutagenesis
  • Polycomb-Group Proteins
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Repressor Proteins / metabolism*
  • STAT5 Transcription Factor
  • Trans-Activators / metabolism

Substances

  • DNA-Binding Proteins
  • Histones
  • Milk Proteins
  • Polycomb-Group Proteins
  • Repressor Proteins
  • STAT5 Transcription Factor
  • Trans-Activators