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In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

2016; Rockefeller University Press; Volume: 213; Issue: 12 Linguagem: Inglês

10.1084/jem.20150821

1540-9538

Alba Azagra, Lidia Román-González, Olga Collazo, Javier Rodríguez‐Ubreva, Virginia G. de Yébenes, Bruna Barneda‐Zahonero, Jairo Rodríguez, Manuel Castro de Moura, Joaquím Grego‐Bessa, Irene Fernández-Duran, Abul Bashar Mir Md. Khademul Islam, Manel Esteller, Almudena R. Ramiro, Esteban Ballestar, Maribel Parra,

Immune Cell Function and Interaction

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.