|
| Status |
Public on Aug 15, 2023 |
| Title |
MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia [TOPmentation data] |
| 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.
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| Overall design |
ChIP-seq
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| |
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| Contributor(s) |
Crump NT, Smith AL, Milne TA |
| Citation(s) |
37626123 |
| |
| Submission date |
May 09, 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 |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (12)
|
| GSM6124609 |
H3K79me3 TOPmentation in DMSO-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124610 |
H3K79me3 TOPmentation in dTAG13-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124611 |
Input for PAF1 TOPmentation in DMSO-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124612 |
PAF1 TOPmentation in DMSO-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124613 |
Input for PAF1 TOPmentation in dTAG13-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124614 |
PAF1 TOPmentation in dTAG13-treated SEM cells with PAF1 endogenously tagged with FKBP12(F36V) |
| GSM6124615 |
H3K79me3 TOPmentation in DMSO-treated SEM cells with SSRP1 endogenously tagged with FKBP12(F36V) |
| GSM6124616 |
H3K79me3 TOPmentation in dTAG13-treated SEM cells with SSRP1 endogenously tagged with FKBP12(F36V) |
| GSM6124617 |
PAF1 TOPmentation in RS4;11 cells |
| GSM6124618 |
PAF1 HT-ChIPmentation in RS4;11 cells |
| GSM6124619 |
ENL TOPmentation in RS4;11 cells |
| GSM6124620 |
ENL HT-ChIPmentation in RS4;11 cells |
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| This SubSeries is part of SuperSeries: |
| GSE202451 |
MLL-AF4 cooperates with PAF1 and FACT to drive high density enhancer interactions in leukemia |
|
| Relations |
| BioProject |
PRJNA836574 |
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