GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE127894 Query DataSets for GSE127894
Status Public on Apr 20, 2022
Title Phosphorylated MED1 Links Transcription Recycling and Cancer Growth
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Mammalian RNA polymerase II (Pol II) initiation, elongation, termination and reinitiation are well studied, but how Pol II dynamically recycles after the transcription cycle remains unclear. By establishing in vitro and in vivo transcription recycling systems, we find that human Mediator 1 (MED1), when phosphorylated at the mammal-specific threonine 1032 by cyclin-dependent kinase 9, dynamically travels with Pol II throughout the transcribed genes to drive Pol II recycling. Mechanistically, MED1 phosphorylation leads to an increase of recycled Pol II via the molecular bridge of MED31, enhancing mRNA output during the transcription recycling process. Importantly, MED1 phosphorylation increases during prostate cancer progression to the lethal phase, and pharmacological inhibition of CDK9 decreases prostate tumor growth through decreasing MED1 phosphorylation and Pol II recycling. Our findings reveal essential mechanisms underlying Pol II recycling and suggest a neglected, yet fundamental Pol II transcription process for therapeutic intervention.
Overall design We have performed time-resolved ChIP-seq of pMED1, Pol2 and histone marks.

We have performed RNA-seq and analyzed transcriptome changes in LNCaP-abl cells treated with vehicle or a CDK9 inhibitor (Atuveciclib).
Contributor(s) Chen Z, Ye Z
Citation(s) 35394046
Submission date Mar 05, 2019
Last update date Apr 23, 2022
Contact name Zhong Chen
Organization name Duke University
Department Pathology
Lab Room 1027B, GSRB1
Street address 905 S. LaSalle Street
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
Platforms (4)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (42)
GSM3656084 ABL_pMed1_Vehicle_rep1_ChIPSeq
GSM3656085 ABL_pMed1_Vehicle_rep2_ChIPSeq
GSM3656086 ABL_Ser2_Vehicle_rep1_ChIPSeq
BioProject PRJNA525738
SRA SRP187834

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
GSE127894_H3K27ac_Abl_comb.norm.bigwig 730.1 Mb (ftp)(http) BIGWIG
GSE127894_H3K36Me3_Abl_comb.norm.bigwig 449.4 Mb (ftp)(http) BIGWIG
GSE127894_H3K4Me2_Abl_comb.norm.bigwig 145.7 Mb (ftp)(http) BIGWIG
GSE127894_H3K4Me3_Abl_comb.norm.bigwig 142.5 Mb (ftp)(http) BIGWIG
GSE127894_RAW.tar 10.3 Gb (http)(custom) TAR (of BIGWIG, BW)
GSE127894_RNA-Seq_results_gene_RPKM.txt.gz 455.4 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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