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

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,...

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Detalles Bibliográficos
Autores: Azagra Rodríguez, Alba, Román González, Lidia, Collazo, Olga, Rodríguez Ubreva, Javier, Yébenes, Virginia G. de, Barneda Zahonero, Bruna, Rodríguez Lumbiarres, Jairo, 1980-, Castro de Moura, Manuel, Grego Bessa, Joaquim, Fernández Duran, Irene, Islam, Abul B. M. M. K., Esteller, Manel, Ramiro, Almudena R., Ballestar Tarín, Esteban, Parra Bola, Mª Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/111110
Acceso en línea:https://hdl.handle.net/2445/111110
Access Level:acceso abierto
Palabra clave:Cèl·lules B
Histones
Limfòcits
Gens
Proteïnes
B cells
Lymphocytes
Genes
Proteins
Descripción
Sumario: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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