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Publication : Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a.

First Author  Kim KY Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  2583
PubMed ID  29968706 Mgi Jnum  J:265029
Mgi Id  MGI:6198981 Doi  10.1038/s41467-018-04818-0
Citation  Kim KY, et al. (2018) Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nat Commun 9(1):2583
abstractText  Embryonic stem cells (ESCs) maintain pluripotency through unique epigenetic states. When ESCs commit to a specific lineage, epigenetic changes in histones and DNA accompany the transition to specialized cell types. Investigating how epigenetic regulation controls lineage specification is critical in order to generate the required cell types for clinical applications. Uhrf1 is a widely known hemi-methylated DNA-binding protein, playing a role in DNA methylation through the recruitment of Dnmt1 and in heterochromatin formation alongside G9a, Trim28, and HDACs. Although Uhrf1 is not essential in ESC self-renewal, it remains elusive how Uhrf1 regulates cell specification. Here we report that Uhrf1 forms a complex with the active trithorax group, the Setd1a/COMPASS complex, to maintain bivalent histone marks, particularly those associated with neuroectoderm and mesoderm specification. Overall, our data demonstrate that Uhrf1 safeguards proper differentiation via bivalent histone modifications.
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