The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis.
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.
Department of Immunology, Research Institute of Molecular Pathology, Vienna Biocenter, Austria.
Roger
R
Revilla-I-Domingo
Ivan
I
Bilic
Bojan
B
Vilagos
Hiromi
H
Tagoh
Anja
A
Ebert
Ido M
IM
Tamir
Leonie
L
Smeenk
Johanna
J
Trupke
Andreas
A
Sommer
Markus
M
Jaritz
Meinrad
M
Busslinger
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse