期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 213, 期 12, 页码 2591-2601出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20150821
关键词
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资金
- Spanish Ministry of Economy and Competitiveness [SAF2011-28290, SAF2014-58228-R]
- ICREA Funding Source: Custom
Class IIa histone deacetylase (HDAC) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows a lymphoid-specific expression pattern within the hematopoietic system. In this study, we explored its potential role in B cell development by generating a conditional knockout mouse model. Our study demonstrates for the first time that HDAC7 deletion dramatically blocks early B cell development and gives rise to a severe lymphopenia in peripheral organs, while also leading to pro-B cell lineage promiscuity. We find that HDAC7 represses myeloid and T lymphocyte genes in B cell progenitors through interaction with myocyte enhancer factor 2C (MEFC2). In B cell progenitors, HDAC7 is recruited to promoters and enhancers of target genes, and its absence leads to increased enrichment of histone active marks. Our results prove that HDAC7 is a bona fide transcriptional repressor essential for B cell development.
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