G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

Tuo Zhang; Ausma Termanis; Burak Özkan; Xun X Bao; Jayne Culley; Flavia de Lima Alves; Juri Rappsilber; Bernard Ramsahoye; Irina Stancheva

doi:10.1016/j.celrep.2016.03.007

G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

Tuo Zhang, Ausma Termanis, Burak Özkan, Xun X Bao, Jayne Culley, Flavia de Lima Alves, Juri Rappsilber, Bernard Ramsahoye, Irina Stancheva

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

Abstract / Description of output

DNA methylation at imprinting control regions (ICRs) is established in gametes in a sex-specific manner and has to be stably maintained during development and in somatic cells to ensure the correct monoallelic expression of imprinted genes. In addition to DNA methylation, the ICRs are marked by allele-specific histone modifications. Whether these marks are essential for maintenance of genomic imprinting is largely unclear. Here, we show that the histone H3 lysine 9 methylases G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells; however, their catalytic activity and the G9a/GLP-dependent H3K9me2 mark are completely dispensable for imprinting maintenance despite the genome-wide loss of non-imprinted DNA methylation in H3K9me2-depleted cells. We provide additional evidence that the G9a/GLP complex protects imprinted DNA methylation by recruitment of de novo DNA methyltransferases, which antagonize TET dioxygenass-dependent erosion of DNA methylation at ICRs.

Original language	English
Pages (from-to)	77-85
Number of pages	9
Journal	Cell Reports
Volume	15
Issue number	1
Early online date	24 Mar 2016
DOIs	https://doi.org/10.1016/j.celrep.2016.03.007
Publication status	Published - Apr 2016

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10.1016/j.celrep.2016.03.007

1-s2.0-S2211124716302480-mainFinal published version, 2.05 MB

Core funding renewal for the Wellcome Trust Centre for Cell Biology
Tollervey, D. & Earnshaw, B.
UK-based charities
1/10/11 → 30/04/17
Project: Research
Epigenetic gene silencing in normal cells and cancer
Stancheva, I.
1/04/08 → 30/09/14
Project: Research

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@article{7d9113b2ca5d48f2b0c77d11af56cdf1,

title = "G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells",

abstract = "DNA methylation at imprinting control regions (ICRs) is established in gametes in a sex-specific manner and has to be stably maintained during development and in somatic cells to ensure the correct monoallelic expression of imprinted genes. In addition to DNA methylation, the ICRs are marked by allele-specific histone modifications. Whether these marks are essential for maintenance of genomic imprinting is largely unclear. Here, we show that the histone H3 lysine 9 methylases G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells; however, their catalytic activity and the G9a/GLP-dependent H3K9me2 mark are completely dispensable for imprinting maintenance despite the genome-wide loss of non-imprinted DNA methylation in H3K9me2-depleted cells. We provide additional evidence that the G9a/GLP complex protects imprinted DNA methylation by recruitment of de novo DNA methyltransferases, which antagonize TET dioxygenass-dependent erosion of DNA methylation at ICRs.",

author = "Tuo Zhang and Ausma Termanis and Burak {\"O}zkan and Bao, {Xun X} and Jayne Culley and {de Lima Alves}, Flavia and Juri Rappsilber and Bernard Ramsahoye and Irina Stancheva",

year = "2016",

month = apr,

doi = "10.1016/j.celrep.2016.03.007",

language = "English",

volume = "15",

pages = "77--85",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

AU - Zhang, Tuo

AU - Termanis, Ausma

AU - Özkan, Burak

AU - Bao, Xun X

AU - Culley, Jayne

AU - de Lima Alves, Flavia

AU - Rappsilber, Juri

AU - Ramsahoye, Bernard

AU - Stancheva, Irina

PY - 2016/4

Y1 - 2016/4

N2 - DNA methylation at imprinting control regions (ICRs) is established in gametes in a sex-specific manner and has to be stably maintained during development and in somatic cells to ensure the correct monoallelic expression of imprinted genes. In addition to DNA methylation, the ICRs are marked by allele-specific histone modifications. Whether these marks are essential for maintenance of genomic imprinting is largely unclear. Here, we show that the histone H3 lysine 9 methylases G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells; however, their catalytic activity and the G9a/GLP-dependent H3K9me2 mark are completely dispensable for imprinting maintenance despite the genome-wide loss of non-imprinted DNA methylation in H3K9me2-depleted cells. We provide additional evidence that the G9a/GLP complex protects imprinted DNA methylation by recruitment of de novo DNA methyltransferases, which antagonize TET dioxygenass-dependent erosion of DNA methylation at ICRs.

AB - DNA methylation at imprinting control regions (ICRs) is established in gametes in a sex-specific manner and has to be stably maintained during development and in somatic cells to ensure the correct monoallelic expression of imprinted genes. In addition to DNA methylation, the ICRs are marked by allele-specific histone modifications. Whether these marks are essential for maintenance of genomic imprinting is largely unclear. Here, we show that the histone H3 lysine 9 methylases G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells; however, their catalytic activity and the G9a/GLP-dependent H3K9me2 mark are completely dispensable for imprinting maintenance despite the genome-wide loss of non-imprinted DNA methylation in H3K9me2-depleted cells. We provide additional evidence that the G9a/GLP complex protects imprinted DNA methylation by recruitment of de novo DNA methyltransferases, which antagonize TET dioxygenass-dependent erosion of DNA methylation at ICRs.

U2 - 10.1016/j.celrep.2016.03.007

DO - 10.1016/j.celrep.2016.03.007

M3 - Article

C2 - 27052169

SN - 2211-1247

VL - 15

SP - 77

EP - 85

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

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Projects

Core funding renewal for the Wellcome Trust Centre for Cell Biology

Epigenetic gene silencing in normal cells and cancer

Cite this