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, 1968-, Ramiro, Almudena R., Ballestar Tarín, Esteban, Parra Bola, Mª Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu: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.