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Title: Cooperative transcriptional repression by BCL6 and BACH2 in germinal center B-cell differentiation      
dateReleased:
11-17-2013
description:
The transcriptional repressors BCL6 and BACH2 are crucial regulators of germinal center (GC) B-cell fate, and are known to interact and repress transcription of PRDM1, a key driver of plasma cell differentiation. How these factors cooperate is not fully understood. Herein we show that while GC formation is only minimally impaired in Bcl6+/- or Bach2+/- mice, double heterozygous Bcl6+/-Bach2+/- mice exhibit profound reduction in GC formation. Splenic B-cells from Bcl6+/- Bach2+/- mice display accelerated plasmacytic differentiation and high expression of key plasma cell genes such as Prdm1, Xbp1 and CD138. ChIP-seq revealed that in B-cells BACH2 is mostly bound to genes together with its heterodimer partner MAFK. The BACH2-MAFK complex binds to sets of genes known to be involved in the GC response, 60% of which are also targets of BCL6. Approximately 30% of BACH2 peaks overlap with BCL6 including cis-regulatory sequences of the PRDM1 gene. BCL6 also modulates BACH2 protein stability and their protein levels are positively correlated in GC B-cells. Therefore, BCL6 and BACH2 cooperate to orchestrate gene expression patterning in GC B cells through both transcriptional and biochemical mechanisms, which collectively determine the proper initiation and timing of terminal differentiation. ChIP-seq using P18 antibodies in OCI-Ly7 cells
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-47784
refinement:
raw
alternateIdentifiers:
47784
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-47784/E-GEOD-47784.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-47784/E-GEOD-47784.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47784
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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