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

School of Medicine

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

37 Citations (Scopus)

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
Pages (from-to)	2583
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04818-0
Publication status	Published - 3 Jul 2018

Keywords

Animals
CCAAT-Enhancer-Binding Proteins
Cellular Reprogramming/genetics
Cellular Reprogramming Techniques
Chimera
DNA Methylation/physiology
Epigenesis, Genetic
Female
Fibroblasts
Gene Knockout Techniques
HEK293 Cells
Histone Code/genetics
Histone-Lysine N-Methyltransferase/genetics
Histones/metabolism
Humans
Male
Mesoderm/cytology
Mice
Mouse Embryonic Stem Cells
Neural Plate/cytology
Nuclear Proteins/genetics
Primary Cell Culture
Recombinant Proteins/genetics
Ubiquitin-Protein Ligases

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10.1038/s41467-018-04818-0

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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), 2583. https://doi.org/10.1038/s41467-018-04818-0

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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.",

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author = "Kun-Yong Kim and Yoshiaki Tanaka and Juan Su and Bilal Cakir and Yangfei Xiang and Benjamin Patterson and Junjun Ding and Yong-Wook Jung and Ji-Hyun Kim and Eriona Hysolli and Haelim Lee and Rana Dajani and Jonghwan Kim and Mei Zhong and Jeong-Heon Lee and David Skalnik and Lim, {Jeong Mook} and Sullivan, {Gareth J} and Jianlong Wang and In-Hyun Park",

year = "2018",

month = jul,

day = "3",

doi = "10.1038/s41467-018-04818-0",

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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, JM, Sullivan, GJ, Wang, J & Park, I-H 2018, 'Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a', Nature Communications, vol. 9, no. 1, pp. 2583. https://doi.org/10.1038/s41467-018-04818-0

TY - JOUR

T1 - Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a

AU - Kim, Kun-Yong

AU - Tanaka, Yoshiaki

AU - Su, Juan

AU - Cakir, Bilal

AU - Xiang, Yangfei

AU - Patterson, Benjamin

AU - Ding, Junjun

AU - Jung, Yong-Wook

AU - Kim, Ji-Hyun

AU - Hysolli, Eriona

AU - Lee, Haelim

AU - Dajani, Rana

AU - Kim, Jonghwan

AU - Zhong, Mei

AU - Lee, Jeong-Heon

AU - Skalnik, David

AU - Lim, Jeong Mook

AU - Sullivan, Gareth J

AU - Wang, Jianlong

AU - Park, In-Hyun

PY - 2018/7/3

Y1 - 2018/7/3

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.

AB - 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.

KW - Animals

KW - CCAAT-Enhancer-Binding Proteins

KW - Cellular Reprogramming/genetics

KW - Cellular Reprogramming Techniques

KW - Chimera

KW - DNA Methylation/physiology

KW - Epigenesis, Genetic

KW - Female

KW - Fibroblasts

KW - Gene Knockout Techniques

KW - HEK293 Cells

KW - Histone Code/genetics

KW - Histone-Lysine N-Methyltransferase/genetics

KW - Histones/metabolism

KW - Humans

KW - Male

KW - Mesoderm/cytology

KW - Mice

KW - Mouse Embryonic Stem Cells

KW - Neural Plate/cytology

KW - Nuclear Proteins/genetics

KW - Primary Cell Culture

KW - Recombinant Proteins/genetics

KW - Ubiquitin-Protein Ligases

U2 - 10.1038/s41467-018-04818-0

DO - 10.1038/s41467-018-04818-0

M3 - Article

C2 - 29968706

SN - 2041-1723

VL - 9

SP - 2583

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

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