MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition

Cell Rep. 2019 Jul 9;28(2):472-485.e5. doi: 10.1016/j.celrep.2019.06.029.

Abstract

The NuRD complex contains both chromatin remodeling and histone deacetylase activities. Mice lacking the MTA2 subunit of NuRD show developmental defects in pro-B, pre-B, immature B, and marginal zone B cells, and abnormal germinal center B cell differentiation during immune responses. Mta2 inactivation also causes a derepression of Igll1 and VpreB1 genes in pre-B cells. Furthermore, MTA2/NuRD interacts directly with AIOLOS/IKAROS and shows a striking overlap with AIOLOS/IKAROS target genes in human pre-B cells, suggesting a functional inter-dependence between MTA2/NuRD and AIOLOS. Mechanistically, MTA2 deficiency in mice leads to increased H3K27 acetylation at both Igll1 and VpreB1 promoters. Gene profiling analyses also identify distinct MTA2-dependent transcription programs in pro-B and pre-B cells. In addition, we find a strong synergy between MTA2 and OCA-B in repressing Igll1 and VpreB1 at the pre-B cell stage, and in regulating both the pre-B to immature B transition and splenic B cell development.

Keywords: AIOLOS; B cell development; Igll1; MTA2; NuRD; OCA-B; chromatin; epigenetics; pre-B cell; transcriptional regulation.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Humans
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics*
  • Mice
  • Precursor Cells, B-Lymphoid / immunology*
  • Repressor Proteins / genetics*
  • Trans-Activators / genetics*

Substances

  • Mta2 protein, mouse
  • Repressor Proteins
  • Trans-Activators
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex