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Publication : Initiation and maintenance of pluripotency gene expression in the absence of cohesin.

First Author  Lavagnolli T Year  2015
Journal  Genes Dev Volume  29
Issue  1 Pages  23-38
PubMed ID  25561493 Mgi Jnum  J:217370
Mgi Id  MGI:5613817 Doi  10.1101/gad.251835.114
Citation  Lavagnolli T, et al. (2015) Initiation and maintenance of pluripotency gene expression in the absence of cohesin. Genes Dev 29(1):23-38
abstractText  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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