@article{a98dfc5b8543492aa8b0045fc82838b3,
title = "Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a",
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.",
author = "Kim, {Kun Yong} and Yoshiaki Tanaka and Juan Su and Bilal Cakir and Yangfei Xiang and Benjamin Patterson and Junjun Ding and Jung, {Yong Wook} and Kim, {Ji Hyun} and Eriona Hysolli and Haelim Lee and Rana Dajani and Jonghwan Kim and Mei Zhong and Lee, {Jeong Heon} and David Skalnik and Lim, {Jeong Mook} and Sullivan, {Gareth J.} and Jianlong Wang and Park, {In Hyun}",
note = "Funding Information: We thank all the Park lab members for their helpful comments and active discussion. We appreciate Dr. Haruhiko Koseki for sharing Uhrf1 KO ESC, and Dr. Nils Neurenkirchen and Dr. Haifan Lin for advice in purifying recombinant Uhrf1. J.W. was partly supported by NIH (R21HD087722). I.H.P. was supported in part by the NIH (GM0099130-01, GM111667-01), the CSCRF (12-SCB-YALE-11, 13-SCB-YALE-06, 16-RMB-Yale-04), the KRIBB/KRCF (NAP-09-3), and a CTSA grant UL1 RR025750 from the National Center for Advancing Translational Science (NCATS), a component of the NIH, and the NIH Roadmap for Medical Research. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH. The sequencing services performed for this study were conducted at Yale Stem Cell Center Genomics Core facility, which was supported by the Connecticut Regenerative Medicine Research Fund and the Li Ka Shing Foundation. Computation time was provided by the Yale University Biomedical High Performance Computing Center. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-04818-0",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}