GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE70000 Query DataSets for GSE70000
Status Public on Jan 04, 2016
Title Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation (RNA-seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The MYC transcription factor is an unstable protein and its turnover is controlled by the ubiquitin system. Ubiquitination enhances MYC-dependent transactivation, but the underlying mechanism remains unresolved. Here we show that proteasomal turnover of MYC is dispensable for recruitment of RNA polymerase II (RNAPII), but is required to promote transcriptional elongation at MYC target genes. Degradation of MYC stimulates histone acetylation and recruitment of BRD4 and P-TEFb to target promoters, leading to phosphorylation of RNAPII CTD and the release of elongating RNAPII. In the absence of degradation, the RNA polymerase II-associated factor (PAF) complex associates with MYC via interaction of its CDC73 subunit with a conserved domain in the amino-terminus of MYC ("MYC box I"), suggesting that a MYC/PAF complex is an intermediate in transcriptional activation. Since histone acetylation depends on a second highly conserved domain in MYCs amino-terminus ("MYC box II"), we propose that both domains co-operate to transfer elongation factors onto paused RNAPII.
Overall design RNA-Seq Experiments were performed in a primary breast epithelial cell line (IMEC).The cell line expressed doxycycline-inducible versions of MYC (WT;Kless,Swap=WTN-KC). Where indicated cells were transfected with siRNAs (siCtrl;siSKP2). Where indicated cells were treaed with the proteasome inhibitor MG132 or EtOH as solvent control. DGE was performed by comparing Dox-treated populations expressing either Dox-inducible MYC or a vector control or comparing Dox-induced cells with EtOH (solvent control) treated cells.
Contributor(s) Jaenicke LA, von Eyss B, Carstensen A, Xu W, Eilers M, Popov N
Citation(s) 26687678
Submission date Jun 18, 2015
Last update date May 15, 2019
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 (47)
GSM1715518 rep1_kless_dox
GSM1715519 rep1_kless_etoh
GSM1715520 rep1_vector_dox
This SubSeries is part of SuperSeries:
GSE70009 Ubiquitin-dependent turnover of MYC promotes loading of the PAF complex on RNA Polymerase II to drive transcriptional elongation
BioProject PRJNA287451
SRA SRP059643

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
GSE70000_RAW.tar 364.6 Mb (http)(custom) TAR (of BEDGRAPH)
GSE70000_rpkm_table_mg_treatment.csv.gz 1.4 Mb (ftp)(http) CSV
GSE70000_rpkm_table_si_skp2.csv.gz 653.7 Kb (ftp)(http) CSV
GSE70000_rpkm_table_wt_kless.csv.gz 2.2 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap