|
| Status |
Public on Jan 03, 2024 |
| Title |
A dual role for CDK-Mediator in controlling Polycomb-dependent topology and priming genes for induction [Hi-C] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Precise control of gene expression is essential for normal development. This is thought to rely on mechanisms that enable communication between gene promoters and other regulatory elements. In embryonic stem cells (ESCs) the CDK-Mediator (CDK-MED) complex has been reported to topologically link gene regulatory elements to enable gene expression and also prime genes for induction during differentiation. Here we discover that CDK-MED contributes little to overall genome organisation in ESCs, but interestingly has a specific and essential role in controlling interactions between inactive gene regulatory elements bound by the Polycomb repressive complexes (PRCs). These interactions are facilitated by CDK-MED but rely on canonical PRC1. However, through separation of function experiments, we reveal that the collaboration between CDK-MED and cPRC1 in creating long-range interactions does not function to prime genes for induction during differentiation. Instead, we discover that priming relies on a topology-independent mechanism whereby the CDK module supports core Mediator engagement with gene promoters to support gene activation.
|
| |
|
| Overall design |
Pofile of genomic distribution of Polycomb (canonical PRC1 and H3K27me3), CDK-Mediator (CDK8) and core Mediator (MED14) was profiled in Med13/13l fl/fl ESCs, in which the CDK-Mediator can be conditionally depleted. Pofile of genomic distribution of CDK-Mediator (CDK8) was profiled in Pcgf4-/-Pcgf2 fl/fl ESCs, in which the canonical PRC1 can be conditionally depleted.
|
| |
|
| Contributor(s) |
van der Weide RH, Klose RJ |
| Citation(s) |
36220895 |
| |
| Submission date |
Nov 10, 2021 |
| Last update date |
Jan 04, 2024 |
| Contact name |
Robin H. van der Weide |
| Organization name |
Hubrecht Institute
|
| Lab |
Kind Lab
|
| Street address |
Uppsalalaan 8
|
| City |
Utrecht |
| State/province |
Utrecht |
| ZIP/Postal code |
3584 CT |
| Country |
Netherlands |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE185930 |
Distinct roles of CKM-Mediator in controlling Polycomb-dependent chromosomal interactions and priming genes for induction |
|
| Relations |
| BioProject |
PRJNA779434 |
| SRA |
SRP345461 |
Less...
More...