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| Status |
Public on May 17, 2012 |
| Title |
ChIP-seq analysis of KAP1 and H3K9me3 modifications in mouse spleen B cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis.
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| Overall design |
Examination of KAP1 binding sites and H3K9me3 enriched regions in KAP1 wild type and KO mouse B splenocytes.
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| Contributor(s) |
Santoni de Sio FR, Kapopoulou A, Trono D |
| Citation(s) |
22452978 |
| Submission date |
Mar 27, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Francesca R. Santoni de Sio |
| E-mail(s) |
santonidesio.francesca@hsr.it
|
| Organization name |
San Raffaele Scientific Institute
|
| Department |
SR-TIGET
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| Lab |
Mechanisms of Peripheral Tolerance
|
| Street address |
via Olgettina 58
|
| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE36880 |
KAP1 regulates gene networks controlling B lymphoid cell differentiation and function |
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| Relations |
| BioProject |
PRJNA157195 |
| SRA |
SRP011995 |
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