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

作者：Kun-Yong Kim, Yoshiaki Tanaka, Juan Su, Bilal Çakir, Yangfei Xiang, Benjamin Patterson, Junjun Ding, Yong-Wook Jung, Ji-Hyun Kim, Eriona Hysolli, Hae-Lim Lee, Rana Dajani, Jonghwan Kim, Mei Zhong, Jeong‐Heon Lee, David G. Skalnik, Jeong Mook Lim, Gareth J. Sullivan, Jianlong Wang, In‐Hyun Park · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-04818-0 · 被引用次数：84 · 研究领域：Epigenetics and DNA Methylation、Cancer-related gene regulation、Genomics and Chromatin Dynamics

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.