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The B‐cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis
Author(s) -
RevillaiDomingo Roger,
Bilic Ivan,
Vilagos Bojan,
Tagoh Hiromi,
Ebert Anja,
Tamir Ido M,
Smeenk Leonie,
Trupke Johanna,
Sommer Andreas,
Jaritz Markus,
Busslinger Meinrad
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.155
Subject(s) - biology , pax5 , enhancer , b cell , transcription factor , gene , lymphopoiesis , regulation of gene expression , histone , genetics , microbiology and biotechnology , progenitor cell , stem cell , antibody
Pax5 controls the identity and development of B cells by repressing lineage‐inappropriate genes and activating B‐cell‐specific genes. Here, we used genome‐wide approaches to identify Pax5 target genes in pro‐B and mature B cells. In these cell types, Pax5 bound to 40% of the cis ‐regulatory elements defined by mapping DNase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8000 target genes, it regulated only 4% of them in pro‐B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5‐regulated genes in pro‐B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro‐B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro‐B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B‐cell identity and function by regulating distinct target genes in early and late B lymphopoiesis.