Transcriptional regulation of BRCA1 expression by a metabolic switch

Autores
Di, Li Jun; Fernandez, Alfonso G.; de Siervi, Adriana; Longo, Dan L.; Gardner, Kevin
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Though the linkages between germline mutations of BRCA1 and hereditary breast cancer are well known, recent evidence suggests that altered BRCA1 transcription may also contribute to sporadic forms of breast cancer. Here we show that BRCA1 expression is controlled by a dynamic equilibrium between transcriptional coactivators and co-repressors that govern histone acetylation and DNA accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor and metabolic sensor, C terminalgbinding protein (CtBP), has a central role in this regulation. Loss of CtBP from the BRCA1 promoter through estrogen induction, depletion by RNA interference or increased NAD + /NADH ratio leads to HDAC1 dismissal, elevated histone acetylation and increased BRCA1 transcription. The active control of chromatin marks, DNA accessibility and gene expression at the BRCA1 promoter by this 'metabolic switch' provides an important molecular link between caloric intake and tumor suppressor expression in mammary cells. © 2010 Nature America, Inc. All rights reserved.
Fil: Di, Li Jun. National Cancer Institute; Estados Unidos
Fil: Fernandez, Alfonso G.. National Cancer Institute; Estados Unidos
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Longo, Dan L.. National Institute on Aging; Estados Unidos
Fil: Gardner, Kevin. National Cancer Institute; Estados Unidos
Materia
Brca1
Ctbp
Breast Cancer
Nadh
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66754
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Transcriptional regulation of BRCA1 expression by a metabolic switchDi, Li JunFernandez, Alfonso G.de Siervi, AdrianaLongo, Dan L.Gardner, KevinBrca1CtbpBreast CancerNadhhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Though the linkages between germline mutations of BRCA1 and hereditary breast cancer are well known, recent evidence suggests that altered BRCA1 transcription may also contribute to sporadic forms of breast cancer. Here we show that BRCA1 expression is controlled by a dynamic equilibrium between transcriptional coactivators and co-repressors that govern histone acetylation and DNA accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor and metabolic sensor, C terminalgbinding protein (CtBP), has a central role in this regulation. Loss of CtBP from the BRCA1 promoter through estrogen induction, depletion by RNA interference or increased NAD + /NADH ratio leads to HDAC1 dismissal, elevated histone acetylation and increased BRCA1 transcription. The active control of chromatin marks, DNA accessibility and gene expression at the BRCA1 promoter by this 'metabolic switch' provides an important molecular link between caloric intake and tumor suppressor expression in mammary cells. © 2010 Nature America, Inc. All rights reserved.Fil: Di, Li Jun. National Cancer Institute; Estados UnidosFil: Fernandez, Alfonso G.. National Cancer Institute; Estados UnidosFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Longo, Dan L.. National Institute on Aging; Estados UnidosFil: Gardner, Kevin. National Cancer Institute; Estados UnidosNature Publishing Group2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66754Di, Li Jun; Fernandez, Alfonso G.; de Siervi, Adriana; Longo, Dan L.; Gardner, Kevin; Transcriptional regulation of BRCA1 expression by a metabolic switch; Nature Publishing Group; Nature Structural and Molecular Biology; 17; 12; 12-2010; 1406-14131545-9985CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb.1941info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nsmb.1941info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:42Zoai:ri.conicet.gov.ar:11336/66754instacron: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 09:52:43.123CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptional regulation of BRCA1 expression by a metabolic switch
title Transcriptional regulation of BRCA1 expression by a metabolic switch
spellingShingle Transcriptional regulation of BRCA1 expression by a metabolic switch
Di, Li Jun
Brca1
Ctbp
Breast Cancer
Nadh
title_short Transcriptional regulation of BRCA1 expression by a metabolic switch
title_full Transcriptional regulation of BRCA1 expression by a metabolic switch
title_fullStr Transcriptional regulation of BRCA1 expression by a metabolic switch
title_full_unstemmed Transcriptional regulation of BRCA1 expression by a metabolic switch
title_sort Transcriptional regulation of BRCA1 expression by a metabolic switch
dc.creator.none.fl_str_mv Di, Li Jun
Fernandez, Alfonso G.
de Siervi, Adriana
Longo, Dan L.
Gardner, Kevin
author Di, Li Jun
author_facet Di, Li Jun
Fernandez, Alfonso G.
de Siervi, Adriana
Longo, Dan L.
Gardner, Kevin
author_role author
author2 Fernandez, Alfonso G.
de Siervi, Adriana
Longo, Dan L.
Gardner, Kevin
author2_role author
author
author
author
dc.subject.none.fl_str_mv Brca1
Ctbp
Breast Cancer
Nadh
topic Brca1
Ctbp
Breast Cancer
Nadh
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Though the linkages between germline mutations of BRCA1 and hereditary breast cancer are well known, recent evidence suggests that altered BRCA1 transcription may also contribute to sporadic forms of breast cancer. Here we show that BRCA1 expression is controlled by a dynamic equilibrium between transcriptional coactivators and co-repressors that govern histone acetylation and DNA accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor and metabolic sensor, C terminalgbinding protein (CtBP), has a central role in this regulation. Loss of CtBP from the BRCA1 promoter through estrogen induction, depletion by RNA interference or increased NAD + /NADH ratio leads to HDAC1 dismissal, elevated histone acetylation and increased BRCA1 transcription. The active control of chromatin marks, DNA accessibility and gene expression at the BRCA1 promoter by this 'metabolic switch' provides an important molecular link between caloric intake and tumor suppressor expression in mammary cells. © 2010 Nature America, Inc. All rights reserved.
Fil: Di, Li Jun. National Cancer Institute; Estados Unidos
Fil: Fernandez, Alfonso G.. National Cancer Institute; Estados Unidos
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Longo, Dan L.. National Institute on Aging; Estados Unidos
Fil: Gardner, Kevin. National Cancer Institute; Estados Unidos
description Though the linkages between germline mutations of BRCA1 and hereditary breast cancer are well known, recent evidence suggests that altered BRCA1 transcription may also contribute to sporadic forms of breast cancer. Here we show that BRCA1 expression is controlled by a dynamic equilibrium between transcriptional coactivators and co-repressors that govern histone acetylation and DNA accessibility at the BRCA1 promoter. Eviction of the transcriptional co-repressor and metabolic sensor, C terminalgbinding protein (CtBP), has a central role in this regulation. Loss of CtBP from the BRCA1 promoter through estrogen induction, depletion by RNA interference or increased NAD + /NADH ratio leads to HDAC1 dismissal, elevated histone acetylation and increased BRCA1 transcription. The active control of chromatin marks, DNA accessibility and gene expression at the BRCA1 promoter by this 'metabolic switch' provides an important molecular link between caloric intake and tumor suppressor expression in mammary cells. © 2010 Nature America, Inc. All rights reserved.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
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/11336/66754
Di, Li Jun; Fernandez, Alfonso G.; de Siervi, Adriana; Longo, Dan L.; Gardner, Kevin; Transcriptional regulation of BRCA1 expression by a metabolic switch; Nature Publishing Group; Nature Structural and Molecular Biology; 17; 12; 12-2010; 1406-1413
1545-9985
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66754
identifier_str_mv Di, Li Jun; Fernandez, Alfonso G.; de Siervi, Adriana; Longo, Dan L.; Gardner, Kevin; Transcriptional regulation of BRCA1 expression by a metabolic switch; Nature Publishing Group; Nature Structural and Molecular Biology; 17; 12; 12-2010; 1406-1413
1545-9985
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/nsmb.1941
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nsmb.1941
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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