Title:
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In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development
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Author:
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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
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Other authors:
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Universitat de Barcelona |
Abstract:
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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. |
Subject(s):
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-Cèl·lules B -Histones -Limfòcits -Gens -Proteïnes -B cells -Histones -Lymphocytes -Genes -Proteins |
Rights:
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(c) Rockefeller University Press, 2016
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Document type:
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Article Article - Published version |
Published by:
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Rockefeller University Press
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