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Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs) and is thought to require de novo association with transcription fa...

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Autores principales: Ferrai, Carmelo, Xie, Sheila Q., Luraghi, Paolo, Munari, Davide, Ramirez, Francisco, Branco, Miguel R., Pombo, Ana, Crippa, Massimo P.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797137/
https://www.ncbi.nlm.nih.gov/pubmed/20052287
http://dx.doi.org/10.1371/journal.pbio.1000270
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author Ferrai, Carmelo
Xie, Sheila Q.
Luraghi, Paolo
Munari, Davide
Ramirez, Francisco
Branco, Miguel R.
Pombo, Ana
Crippa, Massimo P.
author_facet Ferrai, Carmelo
Xie, Sheila Q.
Luraghi, Paolo
Munari, Davide
Ramirez, Francisco
Branco, Miguel R.
Pombo, Ana
Crippa, Massimo P.
author_sort Ferrai, Carmelo
collection PubMed
description The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs) and is thought to require de novo association with transcription factories. We identify two types of factory: “poised transcription factories,” containing RNA polymerase II phosphorylated on Ser5, but not Ser2, residues, which differ from “active factories” associated with phosphorylation on both residues. Using the urokinase-type plasminogen activator (uPA) gene as a model system, we find that this inducible gene is predominantly associated with poised (S5p(+)S2p(−)) factories prior to activation and localized at the CT interior. Shortly after induction, the uPA locus is found associated with active (S5p(+)S2p(+)) factories and loops out from its CT. However, the levels of gene association with poised or active transcription factories, before and after activation, are independent of locus positioning relative to its CT. RNA-FISH analyses show that, after activation, the uPA gene is transcribed with the same frequency at each CT position. Unexpectedly, prior to activation, the uPA loci internal to the CT are seldom transcriptionally active, while the smaller number of uPA loci found outside their CT are transcribed as frequently as after induction. The association of inducible genes with poised transcription factories prior to activation is likely to contribute to the rapid and robust induction of gene expression in response to external stimuli, whereas gene positioning at the CT interior may be important to reinforce silencing mechanisms prior to induction.
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spelling pubmed-27971372010-01-06 Poised Transcription Factories Prime Silent uPA Gene Prior to Activation Ferrai, Carmelo Xie, Sheila Q. Luraghi, Paolo Munari, Davide Ramirez, Francisco Branco, Miguel R. Pombo, Ana Crippa, Massimo P. PLoS Biol Research Article The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs) and is thought to require de novo association with transcription factories. We identify two types of factory: “poised transcription factories,” containing RNA polymerase II phosphorylated on Ser5, but not Ser2, residues, which differ from “active factories” associated with phosphorylation on both residues. Using the urokinase-type plasminogen activator (uPA) gene as a model system, we find that this inducible gene is predominantly associated with poised (S5p(+)S2p(−)) factories prior to activation and localized at the CT interior. Shortly after induction, the uPA locus is found associated with active (S5p(+)S2p(+)) factories and loops out from its CT. However, the levels of gene association with poised or active transcription factories, before and after activation, are independent of locus positioning relative to its CT. RNA-FISH analyses show that, after activation, the uPA gene is transcribed with the same frequency at each CT position. Unexpectedly, prior to activation, the uPA loci internal to the CT are seldom transcriptionally active, while the smaller number of uPA loci found outside their CT are transcribed as frequently as after induction. The association of inducible genes with poised transcription factories prior to activation is likely to contribute to the rapid and robust induction of gene expression in response to external stimuli, whereas gene positioning at the CT interior may be important to reinforce silencing mechanisms prior to induction. Public Library of Science 2010-01-05 /pmc/articles/PMC2797137/ /pubmed/20052287 http://dx.doi.org/10.1371/journal.pbio.1000270 Text en Ferrai et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ferrai, Carmelo
Xie, Sheila Q.
Luraghi, Paolo
Munari, Davide
Ramirez, Francisco
Branco, Miguel R.
Pombo, Ana
Crippa, Massimo P.
Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title_full Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title_fullStr Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title_full_unstemmed Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title_short Poised Transcription Factories Prime Silent uPA Gene Prior to Activation
title_sort poised transcription factories prime silent upa gene prior to activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2797137/
https://www.ncbi.nlm.nih.gov/pubmed/20052287
http://dx.doi.org/10.1371/journal.pbio.1000270
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