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| Status |
Public on Nov 29, 2023 |
| Title |
MYC enhancer invasion promotes prognostic cancer type-specific gene programs through an epigenetic switch [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The transcription factor MYC is overexpressed in most cancers, where it drives multiple hallmarks of cancer progression. MYC is known to promote oncogenic transcription by binding to active promoters. In addition, MYC has also been shown to invade distal enhancers when expressed at oncogenic levels, but this enhancer binding has been proposed to have low gene-regulatory potential. Here, we demonstrate that MYC enhancer binding directly promotes cancer type-specific gene programs predictive of poor patient prognosis. MYC induces transcription of enhancer RNA through recruitment of RNAPII, rather than regulating RNAPII pause-release as is the case at promoters. This is mediated by MYC-induced H3K9 demethylation by KDM3A and acetylation by GCN5, leading to enhancer-specific BRD4 recruitment through its bromodomains, which facilitates RNAPII recruitment. Thus, we propose that MYC drives prognostic cancer type-specific gene programs by promoting RNAPII recruitment to enhancers through induction of an epigenetic switch.
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| Overall design |
RNA-seq during MYC inhibition using KJ-PYR-9 and MYC KD in BT549 triple negative breast cancer cells. RNA-seq during GCN5 inhibition using MB-3 in BT549 triple negative breast cancer cells.
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| Contributor(s) |
Jakobsen ST, Jensen RA, Ravnsborg T, Vaagenso CD, Madsen MS, Andersson R, Jensen ON, Siersbæk R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 06, 2023 |
| Last update date |
Nov 29, 2023 |
| Contact name |
Simon Toftholm Jakobsen |
| E-mail(s) |
simontj@bmb.sdu.dk
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| Organization name |
University of Southern Denmark
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| Department |
Biochemistry and Molecular Biology
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| Lab |
Siersbæk
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| Street address |
Campusvej 55
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| City |
Odense |
| State/province |
Syddanmark |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (24)
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| GSM7027445 |
BT549 cells, DEX treatment, BioRep1 |
| GSM7027446 |
BT549 cells, DEX treatment, BioRep2 |
| GSM7027447 |
BT549 cells, DEX treatment, BioRep3 |
| GSM7027448 |
BT549 cells, KJ-PYR-9 treatment, BioRep1 |
| GSM7027449 |
BT549 cells, KJ-PYR-9 treatment, BioRep2 |
| GSM7027450 |
BT549 cells, KJ-PYR-9 treatment, BioRep3 |
| GSM7027451 |
BT549 cells, KJ-PYR-9 + DEX treatment, BioRep1 |
| GSM7027452 |
BT549 cells, KJ-PYR-9 + DEX treatment, BioRep2 |
| GSM7027453 |
BT549 cells, KJ-PYR-9 + DEX treatment, BioRep3 |
| GSM7027454 |
BT549 cells, siCtl treatment, BioRep1 |
| GSM7027455 |
BT549 cells, siCtl treatment, BioRep2 |
| GSM7027456 |
BT549 cells, siCtl treatment, BioRep3 |
| GSM7027457 |
BT549 cells, siMYC treatment, BioRep1 |
| GSM7027458 |
BT549 cells, siMYC treatment, BioRep2 |
| GSM7027459 |
BT549 cells, siMYC treatment, BioRep3 |
| GSM7729531 |
BT549 cells, VEH treatment, BioRep1 #2 |
| GSM7729532 |
BT549 cells, VEH treatment, BioRep2 #2 |
| GSM7729533 |
BT549 cells, VEH treatment, BioRep3 #2 |
| GSM7729534 |
BT549 cells, MED3 treatment, BioRep1 |
| GSM7729535 |
BT549 cells, MB3 treatment, BioRep2 |
| GSM7729536 |
BT549 cells, MB3 treatment, BioRep3 |
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| This SubSeries is part of SuperSeries: |
| GSE224613 |
MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch |
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| Relations |
| BioProject |
PRJNA934427 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE224611_RAW.tar |
3.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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