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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Gabriele Büchel
  • Anne Carstensen
  • Ka-Yan Mak
  • Isabelle Roeschert
  • Eoin Leen
  • Olga Sumara
  • Julia Hofstetter
  • Steffi Herold
  • Jacqueline Kalb
  • Apoorva Baluapuri
  • Evon Poon
  • Colin Kwok
  • Louis Chesler
  • Hans Michael Maric
  • David S Rickman
  • Elmar Wolf
  • Richard Bayliss
  • Susanne Walz
  • Martin Eilers

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.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind21
Udgave nummer12
Sider (fra-til)3483-3497
Antal sider15
ISSN2211-1247
DOI
StatusUdgivet - 19 dec. 2017

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