Systematic identification of Ctr9 regulome in ERa-positive breast cancer

Ctr9, the key scaffold subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc), has been demonstrated as a positive regulator of ERa-positive breast cancer progression and ERa-target gene expression. Previously, we found that knockdown of Ctr9 reduces ERa protein stability and decreases the occupancy of ERa and RNAPII at select ERa-target genes. However, the genome-wide regulation of the occupancy of ERa and RNAPII mediated by Ctr9 is still unclear. Here, we determined the genome-wide ERa and RNAPII occupancy in response to estrogen induction 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 ERa and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ERa-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ERa and Ctr9 target genes, and further delineates the possible independent function of Ctr9 from other subunits in PAFc. Overall design: ChIP-seq experiments for ERa and RNAPII