Pluto Bioinformatics

GSE113914: Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a [RNA-Seq]

Bulk RNA sequencing

Embryonic stem cells (ESCs) maintain pluripotency through unique epigenetic states. When ESCs commit to a specific cell lineage, changes in histone modifications and DNA methylation accompany the transition to more specialized cell types. Investigating how epigenetic regulation maintains pluripotency is a critical component in order to generate the required cell types for future clinical application. Uhrf1 is a widely known hemi-methylated DNA binding protein, playing a role in heterochromatin formation alongside G9a, Trim28 and HDACs. In addition, it has been demonstrated that Uhrf1 functions to maintain DNA methylation through the recruitment of Dnmt1. Although Uhrf1 is not essential in ESC self-renewal, it still remains elusive how Uhrf1 regulates pluripotency. Here, we set out to elucidate the role of Uhrf1 in pluripotent stem cells. We found that Uhrf1 forms a complex with the active trithoraxgroup oftranscriptional regulators, in particular the Setd1a/COMPASS complex. Our data show that loss of Uhrf1 causes a dramatic reduction of bivalent histone marks, in particular those associated with neuroectoderm and mesoderm specification. Overall, our data demonstrate that Uhrf1 safeguards the balance between pluripotency and differentiation via the Setd1a/COMPASSS complex, through which Uhrf1 mediates bivalent histone modifications. SOURCE: Kun-Yong Kim (kun-yong.kim@yale.edu) - Yale University