4.7 Article

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

期刊

GENES & DEVELOPMENT
卷 32, 期 21-22, 页码 1398-1419

出版社

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.314377.118

关键词

GCN5; MYC; nuclear pore complex; PIN1; Ser62 phosphorylation; transcriptional regulation

资金

  1. Knight National Cancer Institute Cancer Center support grant [P30CA069533]
  2. Prospect Creek Foundation
  3. Brenden-Colson Foundation
  4. [R35GM124704]
  5. [RO1 CA186241]
  6. [RO1 CA100855]
  7. [RO1 CA196228]
  8. [U54 CA209988]
  9. NATIONAL CANCER INSTITUTE [R01CA196228, R01CA100855, U54CA209988, P30CA069533, R01CA186241] Funding Source: NIH RePORTER
  10. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R35GM124704] Funding Source: NIH RePORTER

向作者/读者索取更多资源

The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these control MYC's function on the genome is largely unknown. Recent work demonstrates an intimate connection between nuclear compartmentalization and gene regulation. Here, we report that Ser62 phosphorylation and PIN1-mediated isomerization of MYC dynamically regulate the spatial distribution of MYC in the nucleus, promoting its association with the inner basket of the nuclear pore in response to proliferative signals, where it recruits the histone acetyltransferase GCN5 to bind and regulate local gene acetylation and expression. We demonstrate that PIN1-mediated localization of MYC to the nuclear pore regulates MYC target genes responsive to mitogen stimulation that are involved in proliferation and migration pathways. These changes are also present at the chromatin level, with an increase in open regulatory elements in response to stimulation that is PIN1-dependent and associated with MYC chromatin binding. Taken together, our study indicates that post-translational modification of MYC controls its spatial activity to optimally regulate gene expression in response to extrinsic signals in normal and diseased states.

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