Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. Academic Article uri icon

Overview

abstract

  • MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes in neuroblastoma cells. The analysis shows that N-MYC forms complexes with TFIIIC, TOP2A, and RAD21, a subunit of cohesin. N-MYC and TFIIIC bind to overlapping sites in thousands of Pol II promoters and intergenic regions. TFIIIC promotes association of RAD21 with N-MYC target sites and is required for N-MYC-dependent promoter escape and pause release of Pol II. Aurora-A competes with binding of TFIIIC and RAD21 to N-MYC in vitro and antagonizes association of TOP2A, TFIIIC, and RAD21 with N-MYC during S phase, blocking N-MYC-dependent release of Pol II from the promoter. Inhibition of Aurora-A in S phase restores RAD21 and TFIIIC binding to chromatin and partially restores N-MYC-dependent transcriptional elongation. We propose that complex formation with Aurora-A controls N-MYC function during the cell cycle.

publication date

  • December 19, 2017

Research

keywords

  • Aurora Kinase A
  • N-Myc Proto-Oncogene Protein
  • RNA Polymerase II
  • S Phase

Identity

PubMed Central ID

  • PMC5746598

Scopus Document Identifier

  • 85039965873

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.11.090

PubMed ID

  • 29262328

Additional Document Info

volume

  • 21

issue

  • 12