Cargando…

Systematic identification of Ctr9 regulome in ERα-positive breast cancer

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 r...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Hao, Lu, Li, Chan, Ngai Ting, Horswill, Mark, Ahlquist, Paul, Zhong, Xuehua, Xu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103509/
https://www.ncbi.nlm.nih.gov/pubmed/27829357
http://dx.doi.org/10.1186/s12864-016-3248-3
_version_ 1782466607457501184
author Zeng, Hao
Lu, Li
Chan, Ngai Ting
Horswill, Mark
Ahlquist, Paul
Zhong, Xuehua
Xu, Wei
author_facet Zeng, Hao
Lu, Li
Chan, Ngai Ting
Horswill, Mark
Ahlquist, Paul
Zhong, Xuehua
Xu, Wei
author_sort Zeng, Hao
collection PubMed
description 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 treatment 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3248-3) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5103509
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-51035092016-11-14 Systematic identification of Ctr9 regulome in ERα-positive breast cancer Zeng, Hao Lu, Li Chan, Ngai Ting Horswill, Mark Ahlquist, Paul Zhong, Xuehua Xu, Wei BMC Genomics Research Article 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 treatment 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3248-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-09 /pmc/articles/PMC5103509/ /pubmed/27829357 http://dx.doi.org/10.1186/s12864-016-3248-3 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zeng, Hao
Lu, Li
Chan, Ngai Ting
Horswill, Mark
Ahlquist, Paul
Zhong, Xuehua
Xu, Wei
Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title_full Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title_fullStr Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title_full_unstemmed Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title_short Systematic identification of Ctr9 regulome in ERα-positive breast cancer
title_sort systematic identification of ctr9 regulome in erα-positive breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103509/
https://www.ncbi.nlm.nih.gov/pubmed/27829357
http://dx.doi.org/10.1186/s12864-016-3248-3
work_keys_str_mv AT zenghao systematicidentificationofctr9regulomeinerapositivebreastcancer
AT luli systematicidentificationofctr9regulomeinerapositivebreastcancer
AT channgaiting systematicidentificationofctr9regulomeinerapositivebreastcancer
AT horswillmark systematicidentificationofctr9regulomeinerapositivebreastcancer
AT ahlquistpaul systematicidentificationofctr9regulomeinerapositivebreastcancer
AT zhongxuehua systematicidentificationofctr9regulomeinerapositivebreastcancer
AT xuwei systematicidentificationofctr9regulomeinerapositivebreastcancer