Transcriptomics

Dataset Information

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Chip-chip from pro-B cells with H3K4me3, H3K4me2 and H3K9ac


ABSTRACT: The transcription factor Pax5 represses B-lineage-inappropriate genes and activates B-cell-specific genes in B-lymphocytes. Here we have identified 170 novel Pax5-activated genes. Conditional mutagenesis demonstrated that the Pax5-regulated genes require continuous Pax5 activity for normal expression in pro-B and mature B cells. Expression of half of the Pax5-activated genes is either absent or significantly reduced upon Pax5 loss in plasma cells. Direct Pax5 target genes were identified based on their protein synthesis-independent activation by a Pax5-estrogen receptor fusion protein. Chromatin immunoprecipitation (ChIP) of Pax5 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Pax5 directly activates the chromatin at promoters or putative enhancers of Pax5 target genes. The novel Pax5-activated genes code for key regulatory and structural proteins involved in B cell signaling, adhesion, migration, antigen presentation and germinal center B cell formation, thus revealing a complex regulatory network, which is activated by Pax5 to control B cell development and function. Keywords: Chip-chip, cell type comparison comparison of Pax5-/-Rag2-/- vs Rag2-/- pro-B cells

ORGANISM(S): Mus musculus  

SUBMITTER: Shane McManus  Meinrad Busslinger    

PROVIDER: E-GEOD-15145 | ArrayExpress | 2010-05-20

SECONDARY ACCESSION(S): GSE15145PRJNA114909

REPOSITORIES: GEO, ArrayExpress

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Publications

Stepwise activation of enhancer and promoter regions of the B cell commitment gene Pax5 in early lymphopoiesis.

Decker Thorsten T   Pasca di Magliano Marina M   McManus Shane S   Sun Qiong Q   Bonifer Constanze C   Tagoh Hiromi H   Busslinger Meinrad M  

Immunity 20090402 4


Pax5 is an essential regulator of B cell identity and function. Here, we used transgenesis and deletion mapping to identify a potent enhancer in intron 5 of the Pax5 locus. This enhancer in combination with the promoter region was sufficient to recapitulate the B lymphoid expression of Pax5. The enhancer was silenced by DNA methylation in embryonic stem cells, but became activated in multipotent hematopoietic progenitors. It contained functional binding sites for the transcription factors PU.1,  ...[more]

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