A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer

Yanli Liu, Zhong Wu, Jin Zhou, Dinesh K. A. Ramadurai, Katelyn L. Mortenson, Estrella Aguilera-Jimenez, Yifei Yan, Xiaojun Yang, Alison M. Taylor, Katherine E. Varley, Jason Gertz, Peter S. Choi, Andrew D. Cherniack, Xingdong Chen, Adam J. Bass, Swneke D. Bailey () and Xiaoyang Zhang ()
Additional contact information
Yanli Liu: Fudan University
Zhong Wu: Sichuan University
Jin Zhou: Sichuan University
Dinesh K. A. Ramadurai: University of Utah
Katelyn L. Mortenson: University of Utah
Estrella Aguilera-Jimenez: University of Utah
Yifei Yan: Research Institute of the McGill University Health Centre
Xiaojun Yang: Northwest Agriculture and Forestry University
Alison M. Taylor: Columbia University
Katherine E. Varley: University of Utah
Jason Gertz: University of Utah
Peter S. Choi: University of Pennsylvania
Andrew D. Cherniack: Harvard Medical School
Xingdong Chen: Fudan University
Adam J. Bass: Harvard Medical School
Swneke D. Bailey: Research Institute of the McGill University Health Centre
Xiaoyang Zhang: Fudan University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Amplification and overexpression of the SOX2 oncogene represent a hallmark of squamous cancers originating from diverse tissue types. Here, we find that squamous cancers selectively amplify a 3’ noncoding region together with SOX2, which harbors squamous cancer-specific chromatin accessible regions. We identify a single enhancer e1 that predominantly drives SOX2 expression. Repression of e1 in SOX2-high cells causes collapse of the surrounding enhancers, remarkable reduction in SOX2 expression, and a global transcriptional change reminiscent of SOX2 knockout. The e1 enhancer is driven by a combination of transcription factors including SOX2 itself and the AP-1 complex, which facilitates recruitment of the co-activator BRD4. CRISPR-mediated activation of e1 in SOX2-low cells is sufficient to rebuild the e1-SOX2 loop and activate SOX2 expression. Our study shows that squamous cancers selectively amplify a predominant enhancer to drive SOX2 overexpression, uncovering functional links among enhancer activation, chromatin looping, and lineage-specific copy number amplifications of oncogenes.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27055-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27055-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27055-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().