TitleMTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition.
Publication TypeJournal Article
Year of Publication2019
AuthorsLu, Xiangdong, Chu Chi-Shuen, Fang Terry, Rayon-Estrada Violeta, Fang Fang, Patke Alina, Qian Ye, Clarke Stephen H., Melnick Ari M., Zhang Yi, F Papavasiliou Nina, and Roeder Robert G.
JournalCell Rep
Volume28
Issue2
Pagination472-485.e5
Date Published2019 Jul 09
ISSN2211-1247
KeywordsAnimals, B-Lymphocytes, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Precursor Cells, B-Lymphoid, Repressor Proteins, Trans-Activators
Abstract

<p>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.</p>

DOI10.1016/j.celrep.2019.06.029
Alternate JournalCell Rep
PubMed ID31291582
PubMed Central IDPMC6690613
Grant ListR01 CA178765 / CA / NCI NIH HHS / United States
UL1 TR000043 / TR / NCATS NIH HHS / United States
R01 AR067315 / AR / NIAMS NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States