Cargando…
Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function
Estrogen receptor α (ERα) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. ERα binding activity largely depends on access to binding sites on chromatin, which is facilitated in part by Pioneer Facto...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771234/ https://www.ncbi.nlm.nih.gov/pubmed/31588232 http://dx.doi.org/10.7150/thno.34874 |
_version_ | 1783455655279984640 |
---|---|
author | Jiang, Guojuan Wang, Xinrui Sheng, Dandan Zhou, Lei Liu, Yang Xu, Congling Liu, Suling Zhang, Ji |
author_facet | Jiang, Guojuan Wang, Xinrui Sheng, Dandan Zhou, Lei Liu, Yang Xu, Congling Liu, Suling Zhang, Ji |
author_sort | Jiang, Guojuan |
collection | PubMed |
description | Estrogen receptor α (ERα) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. ERα binding activity largely depends on access to binding sites on chromatin, which is facilitated in part by Pioneer Factors (PFs). Transcription factors operate in complexes through thousands of genomic binding sites in a combinatorial fashion to control the expression of genes. However, the extent of crosstalk and cooperation between ERα pioneer factors and more collaborative transcription factors in breast cancer still remains to be elucidated systematically. Methods: Here, we determined the genomic binding information of 40 transcription-related factors and histone modifications with ChIP-seq in ENCODE and integrated it with other genomic information (RNA-seq, ATAC-seq, Gene microarray, 450k methylation chip, GRO-seq), forming a multi-dimension network to illuminate ERα associated transcription. Results: We show that transcription factor, NR2F2 binds to most sites independently of estrogen. Perturbation of NR2F2 expression decreases ERα DNA binding, chromatin openning, and estrogen-dependent cell growth. In the genome-wide analysis, we show that most binding events of NR2F2 and known pioneer factors FOXA1, GATA3 occur together, covering 85% of the ERα binding sites. Regions bound by all the three TFs appeared to be the most active, to have the strongest ERα binding and to be enriched for the super enhancers. Conclusions: The ERα binds to pre-accessible sites containing ERE elements bound by the three transcription factors (NR2F2, FOXA1 and GATA3).The three genes were also identified to correlate with decreased metastatic potential in patient cohorts and co-regulate each other. Together, our results suggest that NR2F2 is a cofactor with FOXA1 and GATA3 in ERα-mediated transcription. |
format | Online Article Text |
id | pubmed-6771234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-67712342019-10-06 Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function Jiang, Guojuan Wang, Xinrui Sheng, Dandan Zhou, Lei Liu, Yang Xu, Congling Liu, Suling Zhang, Ji Theranostics Research Paper Estrogen receptor α (ERα) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. ERα binding activity largely depends on access to binding sites on chromatin, which is facilitated in part by Pioneer Factors (PFs). Transcription factors operate in complexes through thousands of genomic binding sites in a combinatorial fashion to control the expression of genes. However, the extent of crosstalk and cooperation between ERα pioneer factors and more collaborative transcription factors in breast cancer still remains to be elucidated systematically. Methods: Here, we determined the genomic binding information of 40 transcription-related factors and histone modifications with ChIP-seq in ENCODE and integrated it with other genomic information (RNA-seq, ATAC-seq, Gene microarray, 450k methylation chip, GRO-seq), forming a multi-dimension network to illuminate ERα associated transcription. Results: We show that transcription factor, NR2F2 binds to most sites independently of estrogen. Perturbation of NR2F2 expression decreases ERα DNA binding, chromatin openning, and estrogen-dependent cell growth. In the genome-wide analysis, we show that most binding events of NR2F2 and known pioneer factors FOXA1, GATA3 occur together, covering 85% of the ERα binding sites. Regions bound by all the three TFs appeared to be the most active, to have the strongest ERα binding and to be enriched for the super enhancers. Conclusions: The ERα binds to pre-accessible sites containing ERE elements bound by the three transcription factors (NR2F2, FOXA1 and GATA3).The three genes were also identified to correlate with decreased metastatic potential in patient cohorts and co-regulate each other. Together, our results suggest that NR2F2 is a cofactor with FOXA1 and GATA3 in ERα-mediated transcription. Ivyspring International Publisher 2019-08-21 /pmc/articles/PMC6771234/ /pubmed/31588232 http://dx.doi.org/10.7150/thno.34874 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Jiang, Guojuan Wang, Xinrui Sheng, Dandan Zhou, Lei Liu, Yang Xu, Congling Liu, Suling Zhang, Ji Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title | Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title_full | Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title_fullStr | Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title_full_unstemmed | Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title_short | Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function |
title_sort | cooperativity of co-factor nr2f2 with pioneer factors gata3, foxa1 in promoting erα function |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771234/ https://www.ncbi.nlm.nih.gov/pubmed/31588232 http://dx.doi.org/10.7150/thno.34874 |
work_keys_str_mv | AT jiangguojuan cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT wangxinrui cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT shengdandan cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT zhoulei cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT liuyang cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT xucongling cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT liusuling cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction AT zhangji cooperativityofcofactornr2f2withpioneerfactorsgata3foxa1inpromotingerafunction |