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, 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.
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Alba
A
Azagra
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Lidia
L
Román-González
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Olga
O
Collazo
Chromatin and Disease Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Javier
J
Rodríguez-Ubreva
B Cell Biology Laboratory, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
Virginia G
VG
de Yébenes
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Bruna
B
Barneda-Zahonero
Research and Development Department, qGenomics Laboratory, 08003 Barcelona, Spain.
Jairo
J
Rodríguez
Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Manuel
M
Castro de Moura
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Joaquim
0000-0002-0938-2346
J
Grego-Bessa
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Irene
0000-0003-1289-7276
I
Fernández-Duran
Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.
Abul B M M K
0000-0002-7274-0855
AB
Islam
Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08036 Barcelona, Spain.
Manel
M
Esteller
B Cell Biology Laboratory, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
Almudena R
0000-0002-7539-3844
AR
Ramiro
Chromatin and Disease Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain.
Esteban
E
Ballestar
Cellular Differentiation Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Spain mparra@idibell.cat.
Maribel
M
Parra
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D019070:Cell Lineage; D004742:Enhancer Elements, Genetic / Q000235:genetics; D017353:Gene Deletion; D042421:Histone Code; D006655:Histone Deacetylases / Q000172:deficiency / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; C543274:Hdac7 protein, mouse; D006655:Histone Deacetylases