Mi-2/NuRD chromatin remodeling complexes regulate B and T-lymphocyte development and function

Immunol Rev. 2014 Sep;261(1):126-40. doi: 10.1111/imr.12209.

Abstract

Mi-2/nucleosomal remodeling and deacetylase (NuRD) complexes are important epigenetic regulators of chromatin structure and gene expression. Mi-2/NuRD complexes are an assemblage of proteins that combine key epigenetic regulators necessary for (i) histone deacetylation and demethylation, (ii) binding to methylated DNA, (iii) mobilization of nucleosomes, and (iv) recruitment of additional regulatory proteins. Depending on their context in chromatin, Mi-2/NuRD complexes either activate or repress gene transcription. In this regard, they are important regulators of hematopoiesis and lymphopoiesis. Mi-2/NuRD complexes maintain pools of hematopoietic stem cells. Specifically, components of these complexes control multiple stages of B-cell development by regulating B-cell specific transcription. With one set of components, they inhibit terminal differentiation of germinal center B cells into plasma B cells. They also mediate gene repression together with Blimp-1 during plasma cell differentiation. In cooperation with Ikaros, Mi-2/NuRD complexes also play important roles in T-cell development, including CD4 versus CD8 fate decisions and peripheral T-cell responses. Dysregulation of NuRD during lymphopoiesis promotes leukemogenesis. Here, we review general properties of Mi-2/NuRD complexes and focus on their functions in gene regulation and development of lymphocytes.

Keywords: B cells; T cells; gene regulation; hematopoiesis; lineage commitment/specification; transcription factors.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cell Lineage
  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Cellular
  • Lymphocyte Subsets / immunology*
  • Lymphopoiesis*
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • T-Lymphocytes / immunology*

Substances

  • Mi-2 Nucleosome Remodeling and Deacetylase Complex