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Genes Dev January 1, 2015; 29 (1): 23-38.

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

Lavagnolli T , Gupta P , Hörmanseder E , Mira-Bontenbal H , Dharmalingam G , Carroll T , Gurdon JB , Fisher AG , Merkenschlager M .

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.

PubMed ID: 25561493
PMC ID: PMC4281562
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus
Genes referenced: cd19 cd28 cd37 cd4 cdkn1a h2ax h2axl klf4 lefty lox mdm2 myc pak3 pax5 pou5f3.1 ptprc rad21 rexo1 sox2 tdgf1.3 tp53 ubc ywhaz

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References [+] :
Apostolou, Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. 2013, Pubmed