Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes

Covalent histone modifications clearly play an essential role in ligand-dependent transcriptional regulation by nuclear receptors. One of the predominant mechanisms used by nuclear receptors to activate or repress target-gene transcription is the recruitment of coregulatory factors capable of covale...

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Autores: Tardáguila, Manuel, González-Gugel, Elena, Sánchez-Pacheco, Aurora
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/40278
Acceso en línea:http://hdl.handle.net/10261/40278
Access Level:acceso abierto
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spelling Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genesTardáguila, ManuelGonzález-Gugel, ElenaSánchez-Pacheco, AuroraCovalent histone modifications clearly play an essential role in ligand-dependent transcriptional regulation by nuclear receptors. One of the predominant mechanisms used by nuclear receptors to activate or repress target-gene transcription is the recruitment of coregulatory factors capable of covalently modify the amino terminal ends of histones. Here we show that the thyroid hormone (T3) produces a rapid increase in histone H3Ser10 phosphorylation (H3Ser10ph) concomitant to the rapid displacement of the heterochromatin protein 1β (HP1β) to the nuclear periphery. Moreover, we found that T3-mediated pituitary gene transcription is associated with an increase in H3Ser10ph. Interestingly, the Aurora kinase B inhibitor ZM443979 abolishes the effect of T3 on H3Ser10ph, blocks HP1β delocalization, and significantly reduces ligand-dependent transactivation. Similar effects were shown when Aurora kinase B expression was abrogated in small interfering RNA assays. In an effort to understand the underlying mechanism by which T3 increases H3Ser10ph, we demonstrate that liganded thyroid hormone receptor directly interacts with Aurora kinase B, increasing its kinase activity. Moreover, using chromatin immunoprecipitation assays, we have shown that Aurora kinase B participates of a mechanism that displaces HP1β from promoter region, thus preparing the chromatin for the transcriptional activation of T3 regulated genes. Our findings reveal a novel role for Aurora kinase B during transcriptional initiation in GO/G1, apart from its well-known mitotic activity.This work was supported by Grants BFU2006-13497 and BFU2009-11071 from the Ministerio de Educación y Ciencia and from the Fundación Médica Mutua Madrileña.Peer reviewedEndocrine Society201120112011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/40278reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1210/me.2010-0446info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/402782026-05-22T06:33:51Z
dc.title.none.fl_str_mv Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
title Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
spellingShingle Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
Tardáguila, Manuel
title_short Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
title_full Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
title_fullStr Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
title_full_unstemmed Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
title_sort Aurora kinase B activity is modulated by thyroid hormone during transcriptional activation of pituitary genes
dc.creator.none.fl_str_mv Tardáguila, Manuel
González-Gugel, Elena
Sánchez-Pacheco, Aurora
author Tardáguila, Manuel
author_facet Tardáguila, Manuel
González-Gugel, Elena
Sánchez-Pacheco, Aurora
author_role author
author2 González-Gugel, Elena
Sánchez-Pacheco, Aurora
author2_role author
author
description Covalent histone modifications clearly play an essential role in ligand-dependent transcriptional regulation by nuclear receptors. One of the predominant mechanisms used by nuclear receptors to activate or repress target-gene transcription is the recruitment of coregulatory factors capable of covalently modify the amino terminal ends of histones. Here we show that the thyroid hormone (T3) produces a rapid increase in histone H3Ser10 phosphorylation (H3Ser10ph) concomitant to the rapid displacement of the heterochromatin protein 1β (HP1β) to the nuclear periphery. Moreover, we found that T3-mediated pituitary gene transcription is associated with an increase in H3Ser10ph. Interestingly, the Aurora kinase B inhibitor ZM443979 abolishes the effect of T3 on H3Ser10ph, blocks HP1β delocalization, and significantly reduces ligand-dependent transactivation. Similar effects were shown when Aurora kinase B expression was abrogated in small interfering RNA assays. In an effort to understand the underlying mechanism by which T3 increases H3Ser10ph, we demonstrate that liganded thyroid hormone receptor directly interacts with Aurora kinase B, increasing its kinase activity. Moreover, using chromatin immunoprecipitation assays, we have shown that Aurora kinase B participates of a mechanism that displaces HP1β from promoter region, thus preparing the chromatin for the transcriptional activation of T3 regulated genes. Our findings reveal a novel role for Aurora kinase B during transcriptional initiation in GO/G1, apart from its well-known mitotic activity.
publishDate 2011
dc.date.none.fl_str_mv 2011
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/40278
url http://hdl.handle.net/10261/40278
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1210/me.2010-0446
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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