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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Published inThe Journal of experimental medicine
Main Authors Azagra, Alba, Román González, Lidia, Collazo, Olga, Rodríguez Ubreva, Javier, Yébenes, Virginia G. de, Barneda Zahonero, Bruna, Rodríguez, Jairo, 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
Format Journal Article
LanguageEnglish
Published Rockefeller University Press 01.11.2016
Subjects
B cells
Cèl·lules B
Genes
Gens
Histones
Limfòcits
Lymphocytes
Proteins
Proteïnes
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Summary: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.
ISSN:0022-1007