ZFP281 Recruits MYC to Active Promoters in Regulating Transcriptional Initiation and Elongation

Mol Cell Biol. 2019 Nov 25;39(24):e00329-19. doi: 10.1128/MCB.00329-19. Print 2019 Dec 15.

Abstract

The roles of the MYC transcription factor in transcriptional regulation have been studied intensively. However, the general mechanism underlying the recruitment of MYC to chromatin is less clear. Here, we found that the Krüppel-like transcription factor ZFP281 plays important roles in recruiting MYC to active promoters in mouse embryonic stem cells. At the genome scale, ZFP281 is broadly associated with MYC, and the depletion of ZFP281 significantly reduces the levels of MYC and RNA polymerase II at the ZFP281- and MYC-cobound genes. Specially, we found that recruitment is required for the regulation of the Lin28a oncogene and pri-let-7 transcription. Our results therefore suggest a major role of ZFP281 in recruiting MYC to chromatin and the integration of ZFP281 and the MYC/LIN28A/Let-7 loop into a multilevel circuit.

Keywords: LIN28/Let-7; MYC; ZFP281; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Chromatin / metabolism
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells / metabolism
  • Mice
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Polymerase II / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Transcriptional Elongation Factors
  • Zfp281 protein, mouse
  • RNA Polymerase II