Systematic identification of Ctr9 regulome in ER?-positive breast cancer.

ABSTRACT: BACKGROUND:We had previously identified Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), as a key factor regulating a massive ER? target gene expression and ER?-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ER? protein stability and decreases the occupancy of ER? and RNAPII at a few ER?-target loci. However, it remains to be determined whether Ctr9 controls ER?-target gene expression by regulating the global chromatin occupancy of ER? and RNAPII in the presence of estrogen. RESULTS:In this study, we determined the genome-wide ER? and RNAPII occupancy in response to estrogen reatment and/or Ctr9 knockdown by performing chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). We found that loss of Ctr9 dramatically decreases the global occupancy of ER? and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ER?-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ER? and Ctr9 target genes, and further delineated the independent function of Ctr9 from other subunits in PAFc when regulating transcription. CONCLUSIONS:Our data demonstrated that Ctr9, independent of other PAFc subunits, controls ER?-target gene expression by regulating global chromatin occupancies of ER? and RNAPII.

SUBMITTER: Zeng H 

PROVIDER: S-EPMC5103509 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature