|
| Status |
Public on Dec 16, 2012 |
| Title |
ChIP-seq analysis of KAP1 binding and H3K9me3 modifications in mouse T cell progenitors |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromatin remodelling at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by Kruppel-Associated Box (KRAB)- Associated Protein 1 (KAP1), the universal cofactor of KRAB-zinc finger proteins (-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1-deleted mice displayed a significant expansion of immature thymocytes, imbalances in CD4+/CD8+ cell ratios and impaired responses to TCR stimulation when compared to littermate KAP1 control mice. Transcriptome and chromatin studies revealed that KAP1 binds T cell-specific cis-acting regulatory elements marked by the H3K9me3 repressive mark and enriched in Ikaros/NuRD complexes. Also, KAP1 directly controls the expression of several genes involved in TCR and cytokine signalling. Among these, regulation of FoxO1 seems to play a major role in this system. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB-ZFPs are selectively expressed in T lymphoid cells. These results reveal the so-far unsuspected yet important role of KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation.
|
| |
|
| Overall design |
Examination of KAP1 binding sites and H3K9me3-enriched regions in wild type and KAP1 KO mouse thymocytes.
|
| |
|
| Contributor(s) |
Santoni de Sio FR, Kapopoulou A, Trono D |
| Citation(s) |
22872677 |
| Submission date |
Jun 07, 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
|
| Lab |
Mechanisms of Peripheral Tolerance
|
| Street address |
via Olgettina 58
|
| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE38580 |
KAP1 regulates gene networks controlling T cell development and activation |
|
| Relations |
| BioProject |
PRJNA168176 |
| SRA |
SRP013616 |
Less...
More...