Uhrf1 Regulates Active Transcriptional Marks at Bivalent Domains in Pluripotent Stem Cells Through Setd1a

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jul 4

PMID 29968706

Citations 32

Authors

Kun-Yong Kim

Yoshiaki Tanaka

Juan Su

Bilal Cakir

Yangfei Xiang

Benjamin Patterson

Junjun Ding

Yong-Wook Jung

Ji-Hyun Kim

Eriona Hysolli

Haelim Lee

Rana Dajani

Jonghwan Kim

Mei Zhong

Jeong-Heon Lee

David Skalnik

Jeong Mook Lim

Gareth J Sullivan

Jianlong Wang

In-Hyun Park

Affiliations

Soon will be listed here.

Abstract

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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