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

Cell Rep. 2017 Dec 19;21(12):3483-3497. doi: 10.1016/j.celrep.2017.11.090.


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.

Keywords: Aurora-A; MYC; N-MYC; RAD21; TFIIIC; neuroblastoma; pause release.

MeSH terms

  • Aurora Kinase A / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • DNA Topoisomerases, Type II / metabolism
  • DNA, Intergenic / metabolism
  • DNA-Binding Proteins
  • Humans
  • N-Myc Proto-Oncogene Protein / metabolism*
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • S Phase*
  • Transcription Elongation, Genetic
  • Transcription Factors, TFIII / metabolism


  • Cell Cycle Proteins
  • DNA, Intergenic
  • DNA-Binding Proteins
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Phosphoproteins
  • RAD21 protein, human
  • Transcription Factors, TFIII
  • transcription factor TFIIIC
  • Aurora Kinase A
  • RNA Polymerase II
  • DNA Topoisomerases, Type II