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

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

doi:10.1038/s41467-018-04818-0

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

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	2583
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04818-0
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Kim, K. Y., Tanaka, Y., Su, J., Cakir, B., Xiang, Y., Patterson, B., Ding, J., Jung, Y. W., Kim, J. H., Hysolli, E., Lee, H., Dajani, R., Kim, J., Zhong, M., Lee, J. H., Skalnik, D., Lim, J. M., Sullivan, G. J., Wang, J., & Park, I. H. (2018). Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nature communications, 9(1), Article 2583. https://doi.org/10.1038/s41467-018-04818-0

Kim, KY, Tanaka, Y, Su, J, Cakir, B, Xiang, Y, Patterson, B, Ding, J, Jung, YW, Kim, JH, Hysolli, E, Lee, H, Dajani, R, Kim, J, Zhong, M, Lee, JH, Skalnik, D, Lim, JM, Sullivan, GJ, Wang, J & Park, IH 2018, 'Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a', Nature communications, vol. 9, no. 1, 2583. https://doi.org/10.1038/s41467-018-04818-0

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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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AU - Patterson, Benjamin

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AU - Kim, Jonghwan

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AU - Lee, Jeong Heon

AU - Skalnik, David

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AU - Sullivan, Gareth J.

AU - Wang, Jianlong

AU - Park, In Hyun

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N2 - 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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Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a

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