|
| Status |
Public on Mar 31, 2022 |
| Title |
The histone variant macroH2A1.1 regulates RNA Polymerase II paused genes within defined chromatin interaction landscapes. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The histone variant macroH2A1.1 plays a role in cancer development and metastasis. To determine the underlying molecular mechanisms, we mapped the genome-wide localization of endogenous macroH2A1.1 in the human breast cancer cell line MDA-MB 231. We demonstrate that macroH2A1.1 specifically binds to active promoters and enhancers in addition to facultative heterochromatin. Selective knock-down of macroH2A1.1 deregulates expression of hundreds of highly active genes. Depending on the chromatin landscape, macroH2A1.1 acts through two distinct molecular mechanisms. The first mitigates excessive transcription by binding over domains including the promoter and the gene body. The second stimulates expression of RNA Polymerase II (Pol II) paused genes, including genes regulating mammary tumor cell migration. In contrast to the first one, macroH2A1.1 specifically associates with the TSS of Pol II paused genes. These processes occur in a predefined local 3D genome organization but do not require rewiring of enhancer-promoter contacts. We thus propose that macroH2A1.1 serves as a transcriptional modulator with a potential role in assisting the conversion of promoter-locked into a productive and elongating Pol II.
|
| |
|
| Overall design |
ChIP-seq data against mH2A1.1 and total mH2A1 in MDA-MB 231 cells, combined with RNA-seq and Promoter Capture HiC data in WT and mH2A1.1 KD conditions
|
| |
|
| Contributor(s) |
Recoules L, Sexton T, Karasu N, Mouthair F, Lavigne A, Bystricky K |
| Citation(s) |
35362516 |
| Submission date |
Nov 06, 2019 |
| Last update date |
May 25, 2022 |
| Contact name |
Ludmila Alexandra Recoules |
| E-mail(s) |
recoulesludmila@gmail.com, ludmila.recoules@univ-tlse3.fr
|
| Phone |
0782062835
|
| Organization name |
CNRS
|
| Lab |
CBI
|
| Street address |
69 avenue Marianne Grunberg-Manago, 31062 Toulouse Cedex 9, Toulouse
|
| City |
TOULOUSE |
| ZIP/Postal code |
31062 cedex 9 |
| Country |
France |
| |
|
| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (11)
|
|
| Relations |
| BioProject |
PRJNA588052 |
| SRA |
SRP228798 |
Less...
More...