|
| Status |
Public on Aug 15, 2023 |
| Title |
MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT and loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia, but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.
|
| |
|
| Overall design |
ChIP-seq
|
| |
|
| Contributor(s) |
Crump NT, Smith AL, Milne TA |
| Citation(s) |
37626123 |
| |
| Submission date |
May 07, 2022 |
| Last update date |
Nov 14, 2023 |
| Contact name |
Thomas A Milne |
| E-mail(s) |
thomas.milne@imm.ox.ac.uk
|
| Organization name |
University of Oxford
|
| Department |
MRC Weatherall Institute of Molecular Medicine
|
| Street address |
John Radcliffe Hospital, Headington
|
| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (8)
|
| GSM6122650 |
ChIP seq Input for chALL patient sample 1 |
| GSM6122651 |
MLL ChIP seq for chALL patient sample 1 |
| GSM6122652 |
AF4 ChIP seq for chALL patient sample 1 |
| GSM6122653 |
ChIP seq Input for chALL patient sample 3 |
| GSM6122654 |
MLL ChIP seq for chALL patient sample 3 |
| GSM6122655 |
AF4 ChIP seq for chALL patient sample 3 |
| GSM6122656 |
ChIP seq Input for iALL patient sample 2 |
| GSM6122657 |
MLL ChIP seq for iALL patient sample 2 |
|
| This SubSeries is part of SuperSeries: |
| GSE202451 |
MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia |
|
| Relations |
| BioProject |
PRJNA836128 |
Less...
More...