Details

Autor(en) / Beteiligte

• Lu, Xiangdong
• Chu, Chi-Shuen
• Fang, Terry
• Rayon-Estrada, Violeta
• Fang, Fang
• Patke, Alina
• Qian, Ye
• Clarke, Stephen H
• Melnick, Ari M
• Zhang, Yi
• Papavasiliou, F Nina
• Roeder, Robert G

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2019-07, Vol.28 (2), p.472-485.e5

Ort / Verlag

United States: Elsevier

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.