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Series GSE78957 Query DataSets for GSE78957
Status Public on Dec 20, 2017
Title Association with Aurora-A controls N-MYC-dependent promoter escape and pause release of RNA polymerase II during the cell cycle
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (RNAPII). 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 RNAPII 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 RNAPII. 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 RNAPII 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.
Overall design DNA-binding of N-MYC and TFIIIC upon inhibition of Aurora-A, RNAPII occupancy after shRNA-mediated depletion of TFIIIC5 or in S-phase arrested SH-EP-NMYCER cells and gene expression changes after depletion of RAD21, Aurora-A and TFIIIC5 or activation of NMYC.
Contributor(s) Büchel G, Carstensen A, Mak K, Roeschert I, Leen E, Sumara O, Hofstetter J, Herold S, Kalb J, Baluapuri A, Poon E, Kwok C, Chesler L, Maric HM, Rickman DS, Wolf E, Bayliss R, Walz S, Eilers M
Citation(s) 29262328
Submission date Mar 07, 2016
Last update date Jul 25, 2021
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (50)
GSM2082057 input
GSM2082058 NMyc_DMSO
GSM2082059 NMyc_CD532
BioProject PRJNA314499
SRA SRP071219

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE78957_CD532_4h_vs_DMSO.txt.gz 958.1 Kb (ftp)(http) TXT
GSE78957_CD532_8h_vs_DMSO.txt.gz 984.5 Kb (ftp)(http) TXT
GSE78957_RAW.tar 2.5 Gb (http)(custom) TAR (of BEDGRAPH, WIG)
GSE78957_RNAseq_raw_count_matrix.txt.gz 980.9 Kb (ftp)(http) TXT
GSE78957_SHEP_NMYCER_plusOHT_vs_minusOHT.txt.gz 672.1 Kb (ftp)(http) TXT
GSE78957_siAURKA_vs_siCTR.txt.gz 1012.6 Kb (ftp)(http) TXT
GSE78957_siRAD21_vs_siCTR.txt.gz 973.6 Kb (ftp)(http) TXT
GSE78957_siTF3C5_vs_siCTR.txt.gz 865.6 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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