DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells

Hong Kee Tan; Chan Shuo Wu; Jia Li; Zi Hui Tan; Jordan R. Hoffman; Christopher J. Fry; Henry Yang; Annalisa Di Ruscio; Daniel G. Tenen

doi:10.1093/NAR/GKZ520

DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells

Hong Kee Tan, Chan Shuo Wu, Jia Li, Zi Hui Tan, Jordan R. Hoffman, Christopher J. Fry, Henry Yang, Annalisa Di Ruscio, Daniel G. Tenen

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.

Lingua originale	Inglese
pagine (da-a)	7460-7475
Numero di pagine	16
Rivista	Nucleic Acids Research
Volume	47
Numero di pubblicazione	14
DOI	https://doi.org/10.1093/NAR/GKZ520
Stato di pubblicazione	Pubblicato - 1 ott 2019
Pubblicato esternamente	Sì

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title = "DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells",

abstract = "DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.",

author = "Tan, \{Hong Kee\} and Wu, \{Chan Shuo\} and Jia Li and Tan, \{Zi Hui\} and Hoffman, \{Jordan R.\} and Fry, \{Christopher J.\} and Henry Yang and \{Di Ruscio\}, Annalisa and Tenen, \{Daniel G.\}",

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T1 - DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells

AU - Tan, Hong Kee

AU - Wu, Chan Shuo

AU - Li, Jia

AU - Tan, Zi Hui

AU - Hoffman, Jordan R.

AU - Fry, Christopher J.

AU - Yang, Henry

AU - Di Ruscio, Annalisa

AU - Tenen, Daniel G.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.

AB - DNMT3B is known as a de novo DNA methyltransferase. However, its preferential target sites for DNA methylation are largely unknown. Our analysis on ChIP-seq experiment in human embryonic stem cells (hESC) revealed that DNMT3B, mCA and H3K36me3 share the same genomic distribution profile. Deletion of DNMT3B or its histone-interacting domain (PWWP) demolished mCA in hESCs, suggesting that PWWP domain of DNMT3B directs the formation of mCA landscape. In contrast to the common presumption that PWWP guides DNMT3B-mediated mCG deposition, we found that deleting PWWP does not affect the mCG landscape. Nonetheless, DNMT3B knockout led to the formation of 2985 de novo hypomethylated regions at annotated promoter sites. Upon knockout, most of these promoters gain the bivalent marks, H3K4me3 and H3K27me3. We call them spurious bivalent promoters. Gene ontology analysis associated spurious bivalent promoters with development and cell differentiation. Overall, we found the importance of DNMT3B for shaping the mCA landscape and for maintaining the fidelity of the bivalent promoters in hESCs.

UR - https://www.scopus.com/pages/publications/85071708271

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DO - 10.1093/NAR/GKZ520

M3 - Article

SN - 0305-1048

VL - 47

SP - 7460

EP - 7475

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 14

ER -

DNMT3B shapes the mCA landscape and regulates mCG for promoter bivalency in human embryonic stem cells

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