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

Autor:	Lu X; The Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA., Chu CS; The Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA., Fang T; The Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, USA., Rayon-Estrada V; The Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10065, USA., Fang F; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY 10065, USA., Patke A; The Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065, USA., Qian Y; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Clarke SH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Melnick AM; Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY 10065, USA., Zhang Y; HHMI, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Papavasiliou FN; The Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10065, USA; Division of Immune Diversity, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Roeder RG; The Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: roeder@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Jul 09; Vol. 28 (2), pp. 472-485.e5.
DOI:	10.1016/j.celrep.2019.06.029
Abstrakt:	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. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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