Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation

Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins...

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Detalles Bibliográficos
Autores principales: Bertucci, Paola Yanina, Allo, Mariano, Rocha Viegas, Luciana, Ballaré, Cecilia J., Kornblihtt, Alberto Rodolfo, Vicent, Guillermo Pablo, Pecci, Adali
Publicado: 2013
Materias:
cyclic AMP responsive element binding protein binding protein
histone acetyltransferase
histone acetyltransferase GCN5
histone H3
histone H4
messenger RNA
progesterone receptor
protein bcl x
protein SWI
RNA polymerase II
transcription factor SNF
3' untranslated region
alternative RNA splicing
article
Bcl x gene
binding site
chromatin assembly and disassembly
complex formation
controlled study
exon
gene expression regulation
gene function
gene induction
gene location
gene targeting
histone acetylation
human
human cell
intron
priority journal
transcription elongation
transcription initiation
Alternative Splicing
bcl-X Protein
Binding Sites
Cell Line, Tumor
Chromatin
CREB-Binding Protein
Humans
p300-CBP Transcription Factors
Positive Transcriptional Elongation Factor B
Promegestone
Receptors, Progesterone
RNA Polymerase II
Transcription Elongation, Genetic
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03051048_v41_n12_p6072_Bertucci
http://hdl.handle.net/20.500.12110/paper_03051048_v41_n12_p6072_Bertucci
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role of these sites, we examined the effect of progestins on the transcription of the bcl-x gene, where only intragenic progesterone receptor-binding sites (PRbs) were identified. We found that in response to hormone treatment, the PR is recruited to these sites along with two histone acetyltransferases CREB-binding protein (CBP) and GCN5, leading to an increase in histone H3 and H4 acetylation and to the binding of the SWI/SNF complex. Concomitant, a more relaxed chromatin was detected along bcl-x gene mainly in the regions surrounding the intragenic PRbs. PR also mediated the recruitment of the positive elongation factor pTEFb, favoring RNA polymerase II (Pol II) elongation activity. Together these events promoted the re-distribution of the active Pol II toward the 3′-end of the gene and a decrease in the ratio between proximal and distal transcription. These results suggest a novel mechanism by which PR regulates gene expression by facilitating the proper passage of the polymerase along hormone-dependent genes. © 2013 The Author(s) 2013. Published by Oxford University Press.

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