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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2015
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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. |
format | Online Article Text |
id | pubmed-4281562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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