Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex

Sci Rep. 2017 Sep 14;7(1):11541. doi: 10.1038/s41598-017-11177-1.

Abstract

We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells. Together these reveal for the first time role of TRF2 in REST- repressor complex mediated transcription repression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Co-Repressor Proteins / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Epigenetic Repression*
  • Gene Expression Regulation*
  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Transcription, Genetic

Substances

  • Co-Repressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Nerve Tissue Proteins
  • RCOR1 protein, human
  • Telomeric Repeat Binding Protein 2