Journal article
Amplification of MED30 at chromosome 8q24 reprograms MYC binding to low-affinity oncogenic enhancers in cancer cells
Cell reports (Cambridge), Vol.45(6), 117498
06/11/2026
DOI: 10.1016/j.celrep.2026.117498
PMID: 42275218
Abstract
The activity of many oncogenic transcription factors (TFs) is constrained by enhancer binding-site affinity, leaving many low-affinity sites unoccupied under physiological conditions. Whether coactivator amplification in cancer redirects TFs to these sites is unclear. Here, we show that amplification of MED30, a Mediator subunit at 8q24, promotes aberrant MYC binding to low-affinity regulatory regions and is associated with poor outcomes. Besides frequent MYC MED30 co-amplification, MED30 overexpression alone is sufficient to enable MYC occupancy and activation of previously weak or unbound enhancers and promoters, driving tumor-promoting gene expression. Functional studies in pancreatic ductal adenocarcinoma and glioblastoma demonstrate that MED30 is oncogenic and serves as a prognostic marker independent of MYC amplification. These findings reveal a cofactor-driven mechanism by which MED30 licenses MYC binding to low-affinity sites, reprogramming enhancers during cancer progression with therapeutic implications.
Details
- Title: Subtitle
- Amplification of MED30 at chromosome 8q24 reprograms MYC binding to low-affinity oncogenic enhancers in cancer cells
- Creators
- Chunyu Jin - University of California San DiegoLinjie Zhao - UPMC Hillman Cancer CenterWubin Ma - University of California San DiegoGuofeng Zhao - University of California San DiegoYujia Liu - University of California San DiegoHanwen Zhang - University of California San DiegoShenghong Ma - National Foundation for Cancer ResearchLikun Yao - University of California San DiegoYuan Liu - University of California San DiegoQiulian Wu - UPMC Hillman Cancer CenterHuairui Yuan - UPMC Hillman Cancer CenterKailin Yang - Cleveland ClinicWei Yuan - University of California San DiegoKenneth Ohgi - University of California San DiegoJeremy N Rich - University of Pittsburgh Medical CenterMichael G Rosenfeld - University of California San Diego
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.45(6), 117498
- DOI
- 10.1016/j.celrep.2026.117498
- PMID
- 42275218
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier
- Grant note
- NIH: DK018477, DK039949, HL150521, NS103434, CA197718, CA238662, CA268634 NIH/NCI K22 award: K22CA255404 National Institutes of Health SIG grant: S10 OD026929
We thank Dr. Thomas G. Boyer (University of Texas Health Science Center at San Antonio) for MED30 and MED4 antibodies, Diwen Gan (UCSD) for help in motif analysis, and Janet Hightower for assistance with figure preparation. This work is supported by NIH grants (DK018477, DK039949, and HL150521) to M.G.R., by NIH grants (NS103434, CA197718, CA238662, and CA268634) to J.N.R., and by NIH/NCI K22 award (K22CA255404) to C.J. This publication includes data generated at the UC San Diego IGM Genomics Center utilizing an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929) .
- Language
- English
- Date published
- 06/11/2026
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9985174612302771
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