Systematic identification of Ctr9 regulome in ERα-positive breast cancer.
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 ERα target gene expression and ERα-positive breast cancer growth. Furthermore, we have shown that knockdown of Ctr9 reduces ERα protein stability and decreases the occupancy of ERα and RNAPII at a few ERα-target loci. However, it remains to be determined whether Ctr9 controls ERα-target gene expression by regulating the global chromatin occupancy of ERα and RNAPII in the presence of estrogen.



In this study, we determined the genome-wide ERα 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 ERα and RNAPII, highlighting the significance of Ctr9 in regulating estrogen signaling in ERα-positive breast cancer cells. Combining this resource with previously published genomic data sets, we identified a unique subset of ERα and Ctr9 target genes, and further delineated the independent function of Ctr9 from other subunits in PAFc when regulating transcription.



Our data demonstrated that Ctr9, independent of other PAFc subunits, controls ERα-target gene expression by regulating global chromatin occupancies of ERα and RNAPII.
McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.|Present address: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, 181 Massachusetts Avenue, Cambridge, MA, 02139, USA.
Hao
H
Zeng
Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Li
L
Lu
McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Ngai Ting
NT
Chan
Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Mark
M
Horswill
McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.|Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.|Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Paul
P
Ahlquist
Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA. xuehua.zhong@wisc.edu.
Xuehua
X
Zhong
McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA. wxu@oncology.wisc.edu.
Wei
W
Xu
D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D059372:Nucleotide Motifs; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors; D059467:Transcriptome
C484387:CTR9 protein, human; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors
Breast cancer; Ctr9; Estrogen receptor α; Genome-wide profiling; RNA polymerase II