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Initiation and maintenance of pluripotency gene expression in the absence of cohesin

Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin’s contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the...

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Autores principales: Lavagnolli, Thais, Gupta, Preksha, Hörmanseder, Eva, Mira-Bontenbal, Hegias, Dharmalingam, Gopuraja, Carroll, Thomas, Gurdon, John B., Fisher, Amanda G., Merkenschlager, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281562/
https://www.ncbi.nlm.nih.gov/pubmed/25561493
http://dx.doi.org/10.1101/gad.251835.114
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author Lavagnolli, Thais
Gupta, Preksha
Hörmanseder, Eva
Mira-Bontenbal, Hegias
Dharmalingam, Gopuraja
Carroll, Thomas
Gurdon, John B.
Fisher, Amanda G.
Merkenschlager, Matthias
author_facet Lavagnolli, Thais
Gupta, Preksha
Hörmanseder, Eva
Mira-Bontenbal, Hegias
Dharmalingam, Gopuraja
Carroll, Thomas
Gurdon, John B.
Fisher, Amanda G.
Merkenschlager, Matthias
author_sort Lavagnolli, Thais
collection PubMed
description Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin’s contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells, which promoted DNA replication-dependent reprogramming of somatic fusion partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in heterokaryons, due in part to defective DNA replication. Pluripotency gene induction was rescued by Myc, which restored DNA replication, and by nuclear transfer, where reprogramming does not require DNA replication. These results redefine cohesin’s role in pluripotency and reveal a novel function for Myc in promoting the replication-dependent reprogramming of somatic nuclei.
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spelling pubmed-42815622015-07-01 Initiation and maintenance of pluripotency gene expression in the absence of cohesin Lavagnolli, Thais Gupta, Preksha Hörmanseder, Eva Mira-Bontenbal, Hegias Dharmalingam, Gopuraja Carroll, Thomas Gurdon, John B. Fisher, Amanda G. Merkenschlager, Matthias Genes Dev Research Paper Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin’s contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells, which promoted DNA replication-dependent reprogramming of somatic fusion partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in heterokaryons, due in part to defective DNA replication. Pluripotency gene induction was rescued by Myc, which restored DNA replication, and by nuclear transfer, where reprogramming does not require DNA replication. These results redefine cohesin’s role in pluripotency and reveal a novel function for Myc in promoting the replication-dependent reprogramming of somatic nuclei. Cold Spring Harbor Laboratory Press 2015-01-01 /pmc/articles/PMC4281562/ /pubmed/25561493 http://dx.doi.org/10.1101/gad.251835.114 Text en © 2015 Lavagnolli et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Lavagnolli, Thais
Gupta, Preksha
Hörmanseder, Eva
Mira-Bontenbal, Hegias
Dharmalingam, Gopuraja
Carroll, Thomas
Gurdon, John B.
Fisher, Amanda G.
Merkenschlager, Matthias
Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title_full Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title_fullStr Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title_full_unstemmed Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title_short Initiation and maintenance of pluripotency gene expression in the absence of cohesin
title_sort initiation and maintenance of pluripotency gene expression in the absence of cohesin
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281562/
https://www.ncbi.nlm.nih.gov/pubmed/25561493
http://dx.doi.org/10.1101/gad.251835.114
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