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Updated: Mar 12, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Systematic identification of Ctr9 regulome in ERα-positive breast cancer
Hao Zeng1,2, Li Lu3, Ngai Ting Chan1
1McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA.
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 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.
Results:
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.
Conclusions:
Our data demonstrated that Ctr9, independent of other PAFc subunits, controls ERα-target gene expression by regulating global chromatin occupancies of ERα and RNAPII.
Insights
Ctr9 regulates estrogen receptor alpha (ERα) target gene expression by controlling global chromatin occupancy of ERα and RNA polymerase II (RNAPII). This finding is crucial for understanding ERα-positive breast cancer growth.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Ctr9 is a key subunit of the human RNA polymerase II (RNAPII) associated factor complex (PAFc).
- Previous studies identified Ctr9 as a regulator of ERα target gene expression and ERα-positive breast cancer growth.
- Ctr9 knockdown reduces ERα protein stability and RNAPII occupancy at specific ERα target genes.
Purpose of the Study:
- To determine if Ctr9 controls ERα target gene expression by regulating global chromatin occupancy of ERα and RNAPII.
- To investigate the role of Ctr9 in estrogen signaling in ERα-positive breast cancer cells.
Main Methods:
- Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) was used.
- Genome-wide ERα and RNAPII occupancy was determined in response to estrogen and/or Ctr9 knockdown.
- Genomic data sets were combined to identify ERα and Ctr9 target genes.
Main Results:
- Loss of Ctr9 significantly decreases global ERα and RNAPII occupancy.
- This highlights Ctr9's importance in regulating estrogen signaling in ERα-positive breast cancer.
- A unique subset of ERα and Ctr9 target genes was identified, revealing Ctr9's independent function.
Conclusions:
- Ctr9 controls ERα target gene expression independently of other PAFc subunits.
- Ctr9 regulates global chromatin occupancies of ERα and RNAPII, impacting gene expression.
