Tissue-specific inactivation of HAT cofactor TRRAP reveals its essential role in B cells

Cell Cycle. 2014;13(10):1583-9. doi: 10.4161/cc.28560. Epub 2014 Mar 18.

Abstract

The transformation/transcription domain-associated protein (TRRAP) is a common component of many histone acetyltransferase (HAT) complexes. Targeted-deletion of the Trrap gene led to early embryonic lethality and revealed a critical function of TRRAP in cell proliferation. Here, we investigate the function of TRRAP in murine B cells. To this end, we ablated Trrap gene in a B cell-restricted manner and studied its impact on B-cell development and proliferation, a pre-requisite for class switch recombination (CSR), the process that allows IgM-expressing B lymphocytes to switch to the expression of IgG, IgE, or IgA isotypes. We show that TRRAP deficiency impairs B-cell development but does not directly affect CSR. Instead, cells induced to proliferate undergo apoptosis. Our findings demonstrate a central and general role of TRRAP in cell proliferation.

Keywords: B lymphocyte; TRRAP; class switch recombination; immunoglobulin gene; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Proliferation
  • Histone Acetyltransferases / metabolism*
  • Immunoglobulin Class Switching
  • Mice, Mutant Strains
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Organ Specificity

Substances

  • Adaptor Proteins, Signal Transducing
  • Nuclear Proteins
  • transformation-transcription domain-associated protein
  • Histone Acetyltransferases