Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesion 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, cohesion 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 replicationdependent 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.

Cohesin, Embryonic stem cells, Heterokaryon, Nuclear transfer, Pluripotency, Reprogramming,
Genes & Development
Department of Developmental Biology

Lavagnolli, T, Gupta, P, Hörmanseder, E, Mira-Bontenbal, H, Dharmalingam, G, Carroll, T, … Merkenschlager, M. (2015). Initiation and maintenance of pluripotency gene expression in the absence of cohesin. Genes & Development, 29(1), 23–38. doi:10.1101/gad.251835.114