Format

Send to

Choose Destination
Nat Genet. 2019 Dec;51(12):1723-1731. doi: 10.1038/s41588-019-0535-3. Epub 2019 Nov 29.

WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating.

Author information

1
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Bioclinicum, Solna, Sweden.
2
Bio Systems Design Department, Bio Analytical Systems Product Division, Analytical & Medical Solution Business Group, Hitachi High Technologies, Hitachinaka, Ibaraki, Japan.
3
Department of Computer Science and Information Technology, University of Kotli Azad Jammu and Kashmir, Kotli, Pakistan.
4
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Bioclinicum, Solna, Sweden. anita.gondor@ki.se.
5
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Bioclinicum, Solna, Sweden. rolf.ohlsson@ki.se.

Abstract

WNT signaling activates MYC expression in cancer cells. Here we report that this involves an oncogenic super-enhancer-mediated tethering of active MYC alleles to nuclear pores to increase transcript export rates. As the decay of MYC transcripts is more rapid in the nucleus than in the cytoplasm, the oncogenic super-enhancer-facilitated export of nuclear MYC transcripts expedites their escape from the nuclear degradation system in colon cancer cells. The net sum of this process, as supported by computer modeling, is greater cytoplasmic MYC messenger RNA levels in colon cancer cells than in wild type cells. The cancer-cell-specific gating of MYC is regulated by AHCTF1 (also known as ELYS), which connects nucleoporins to the oncogenic super-enhancer via β-catenin. We conclude that WNT signaling collaborates with chromatin architecture to post-transcriptionally dysregulate the expression of a canonical cancer driver.

PMID:
31784729
DOI:
10.1038/s41588-019-0535-3

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center