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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Dec 21

PMID 29262328

Citations 51

Authors

Gabriele Buchel

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

Affiliations

Soon will be listed here.

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.

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