Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells

Autores
la Greca, Alejandro Damián; Bellora, Nicolás; Le Dily, François; Jara, Rodrigo Agustin; Nacht, Ana Silvina; Quilez Oliete, Javier; Villanueva, José Luis; Vidal, Enrique; Merino, Gabriela; Fresno, Cristóbal; Tarifa Reischle, Inti Carlos; Vallejo, Griselda; Vicent, Guillermo Pablo; Fernández, Elmer; Beato, Miguel; Saragueta, Patricia Esther
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call "progestin control regions" (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.
Fil: la Greca, Alejandro Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le Dily, François. Centro de Regulación Genómica; España
Fil: Jara, Rodrigo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Nacht, Ana Silvina. Centro de Regulación Genómica; España
Fil: Quilez Oliete, Javier. Centro de Regulación Genómica; España
Fil: Villanueva, José Luis. Centro de Regulación Genómica; España
Fil: Vidal, Enrique. Centro de Regulación Genómica; España
Fil: Merino, Gabriela. No especifíca;
Fil: Fresno, Cristóbal. No especifíca;
Fil: Tarifa Reischle, Inti Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vallejo, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vicent, Guillermo Pablo. Centro de Regulación Genómica; España
Fil: Fernández, Elmer. No especifíca;
Fil: Beato, Miguel. Centro de Regulación Genómica; España
Fil: Saragueta, Patricia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
steroid receptors
gene regulation
endometrial cancer
ChIPseq
progesterone receptor
estrogen receptor
pax2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/213157
Acceder
id CONICETDig_39715128f9ced02046ca689f7236feb9
oai_identifier_str oai:ri.conicet.gov.ar:11336/213157
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cellsla Greca, Alejandro DamiánBellora, NicolásLe Dily, FrançoisJara, Rodrigo AgustinNacht, Ana SilvinaQuilez Oliete, JavierVillanueva, José LuisVidal, EnriqueMerino, GabrielaFresno, CristóbalTarifa Reischle, Inti CarlosVallejo, GriseldaVicent, Guillermo PabloFernández, ElmerBeato, MiguelSaragueta, Patricia Esthersteroid receptorsgene regulationendometrial cancerChIPseqprogesterone receptorestrogen receptorpax2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call "progestin control regions" (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.Fil: la Greca, Alejandro Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Le Dily, François. Centro de Regulación Genómica; EspañaFil: Jara, Rodrigo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nacht, Ana Silvina. Centro de Regulación Genómica; EspañaFil: Quilez Oliete, Javier. Centro de Regulación Genómica; EspañaFil: Villanueva, José Luis. Centro de Regulación Genómica; EspañaFil: Vidal, Enrique. Centro de Regulación Genómica; EspañaFil: Merino, Gabriela. No especifíca;Fil: Fresno, Cristóbal. No especifíca;Fil: Tarifa Reischle, Inti Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vallejo, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vicent, Guillermo Pablo. Centro de Regulación Genómica; EspañaFil: Fernández, Elmer. No especifíca;Fil: Beato, Miguel. Centro de Regulación Genómica; EspañaFil: Saragueta, Patricia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaeLife Sciences Publications2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/213157la Greca, Alejandro Damián; Bellora, Nicolás; Le Dily, François; Jara, Rodrigo Agustin; Nacht, Ana Silvina; et al.; Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells; eLife Sciences Publications; eLife; 11; 1-2022; 1-312050-084XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/66034info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.66034info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:15Zoai:ri.conicet.gov.ar:11336/213157instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:15.835CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
title Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
spellingShingle Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
la Greca, Alejandro Damián
steroid receptors
gene regulation
endometrial cancer
ChIPseq
progesterone receptor
estrogen receptor
pax2
title_short Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
title_full Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
title_fullStr Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
title_full_unstemmed Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
title_sort Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells
dc.creator.none.fl_str_mv la Greca, Alejandro Damián
Bellora, Nicolás
Le Dily, François
Jara, Rodrigo Agustin
Nacht, Ana Silvina
Quilez Oliete, Javier
Villanueva, José Luis
Vidal, Enrique
Merino, Gabriela
Fresno, Cristóbal
Tarifa Reischle, Inti Carlos
Vallejo, Griselda
Vicent, Guillermo Pablo
Fernández, Elmer
Beato, Miguel
Saragueta, Patricia Esther
author la Greca, Alejandro Damián
author_facet la Greca, Alejandro Damián
Bellora, Nicolás
Le Dily, François
Jara, Rodrigo Agustin
Nacht, Ana Silvina
Quilez Oliete, Javier
Villanueva, José Luis
Vidal, Enrique
Merino, Gabriela
Fresno, Cristóbal
Tarifa Reischle, Inti Carlos
Vallejo, Griselda
Vicent, Guillermo Pablo
Fernández, Elmer
Beato, Miguel
Saragueta, Patricia Esther
author_role author
author2 Bellora, Nicolás
Le Dily, François
Jara, Rodrigo Agustin
Nacht, Ana Silvina
Quilez Oliete, Javier
Villanueva, José Luis
Vidal, Enrique
Merino, Gabriela
Fresno, Cristóbal
Tarifa Reischle, Inti Carlos
Vallejo, Griselda
Vicent, Guillermo Pablo
Fernández, Elmer
Beato, Miguel
Saragueta, Patricia Esther
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv steroid receptors
gene regulation
endometrial cancer
ChIPseq
progesterone receptor
estrogen receptor
pax2
topic steroid receptors
gene regulation
endometrial cancer
ChIPseq
progesterone receptor
estrogen receptor
pax2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call "progestin control regions" (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.
Fil: la Greca, Alejandro Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bellora, Nicolás. Comision Nacional de Energia Atomica. Gerencia de Area de Aplicaciones de la Tecnologia Nuclear. Instituto de Tecnologias Nucleares Para la Salud.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le Dily, François. Centro de Regulación Genómica; España
Fil: Jara, Rodrigo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Nacht, Ana Silvina. Centro de Regulación Genómica; España
Fil: Quilez Oliete, Javier. Centro de Regulación Genómica; España
Fil: Villanueva, José Luis. Centro de Regulación Genómica; España
Fil: Vidal, Enrique. Centro de Regulación Genómica; España
Fil: Merino, Gabriela. No especifíca;
Fil: Fresno, Cristóbal. No especifíca;
Fil: Tarifa Reischle, Inti Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vallejo, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vicent, Guillermo Pablo. Centro de Regulación Genómica; España
Fil: Fernández, Elmer. No especifíca;
Fil: Beato, Miguel. Centro de Regulación Genómica; España
Fil: Saragueta, Patricia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Estrogen (E2) and Progesterone (Pg), via their specific receptors (ERalpha and PR), are major determinants in the development and progression of endometrial carcinomas, However, their precise mechanism of action and the role of other transcription factors involved are not entirely clear. Using Ishikawa endometrial cancer cells, we report that E2 treatment exposes a set of progestin-dependent PR binding sites which include both E2 and progestin target genes. ChIP-seq results from hormone-treated cells revealed a non-random distribution of PAX2 binding in the vicinity of these estrogen-promoted PR sites. Altered expression of hormone regulated genes in PAX2 knockdown cells suggests a role for PAX2 in fine-tuning ERalpha and PR interplay in transcriptional regulation. Analysis of long-range interactions by Hi-C coupled with ATAC-seq data showed that these regions, that we call "progestin control regions" (PgCRs), exhibited an open chromatin state even before hormone exposure and were non-randomly associated with regulated genes. Nearly 20% of genes potentially influenced by PgCRs were found to be altered during progression of endometrial cancer. Our findings suggest that endometrial response to progestins in differentiated endometrial tumor cells results in part from binding of PR together with PAX2 to accessible chromatin regions. What maintains these regions open remains to be studied.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/213157
la Greca, Alejandro Damián; Bellora, Nicolás; Le Dily, François; Jara, Rodrigo Agustin; Nacht, Ana Silvina; et al.; Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells; eLife Sciences Publications; eLife; 11; 1-2022; 1-31
2050-084X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/213157
identifier_str_mv la Greca, Alejandro Damián; Bellora, Nicolás; Le Dily, François; Jara, Rodrigo Agustin; Nacht, Ana Silvina; et al.; Chromatin topology defines estradiol-primed progesterone receptor and PAX2 binding in endometrial cancer cells; eLife Sciences Publications; eLife; 11; 1-2022; 1-31
2050-084X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://elifesciences.org/articles/66034
info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.66034
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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