Systematic identification of Ctr9 regulome in ERα-positive breast cancer.

Autor:	Zeng H; 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., Lu L; Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA., Chan NT; McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA., Horswill M; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, 53706, USA., Ahlquist P; 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., Zhong X; Laboratory of Genetics & Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53706, USA. xuehua.zhong@wisc.edu., Xu W; McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI, 53706, USA. wxu@oncology.wisc.edu.
Jazyk:	angličtina
Zdroj:	BMC genomics [BMC Genomics] 2016 Nov 09; Vol. 17 (1), pp. 902. Date of Electronic Publication: 2016 Nov 09.
DOI:	10.1186/s12864-016-3248-3
Abstrakt:	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.
Databáze:	MEDLINE
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