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The B cell identity factor Pax5 regulates distinct transcriptional programs in early and late B lymphopoiesis


ABSTRACT: 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 8,000 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. 44 samples (16 RNA-seq, 15 ChIP-seq, 6 DHS-seq, 5 Bio-ChIP-seq, 2 CAGE-seq). All but four samples in in 2 biological replicates (8819, 8275, 8095, 8666). WT and experimental samples are provided.

ORGANISM(S): Mus musculus

SUBMITTER: Meinrad Busslinger 

PROVIDER: E-GEOD-38046 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis.

Revilla-I-Domingo Roger R   Bilic Ivan I   Vilagos Bojan B   Tagoh Hiromi H   Ebert Anja A   Tamir Ido M IM   Smeenk Leonie L   Trupke Johanna J   Sommer Andreas A   Jaritz Markus M   Busslinger Meinrad M  

The EMBO journal 20120605 14


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  ...[more]

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