Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus

Anders M. Lindroth, Jung Park Yoon, Chelsea M. McLean, Gregoriy A. Dokshin, Jenna M. Persson, Herry Herman, Diego Pasini, Xavier Miró, Mary E. Donohoe, Jeannie T. Lee, Kristian Helin, Paul D. Soloway

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.

Original languageEnglish
Article numbere1000145
JournalPLoS Genetics
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 2008

Fingerprint

ras-GRF1
antagonism
methylation
DNA methylation
DNA Methylation
DNA
loci
epigenetics
Epigenomics
Mothers
Azacitidine
Methylation
genetically modified organisms
Embryonic Structures

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Lindroth, A. M., Yoon, J. P., McLean, C. M., Dokshin, G. A., Persson, J. M., Herman, H., ... Soloway, P. D. (2008). Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus. PLoS Genetics, 4(8), [e1000145]. https://doi.org/10.1371/journal.pgen.1000145

Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus. / Lindroth, Anders M.; Yoon, Jung Park; McLean, Chelsea M.; Dokshin, Gregoriy A.; Persson, Jenna M.; Herman, Herry; Pasini, Diego; Miró, Xavier; Donohoe, Mary E.; Lee, Jeannie T.; Helin, Kristian; Soloway, Paul D.

In: PLoS Genetics, Vol. 4, No. 8, e1000145, 08.2008.

Research output: Contribution to journalArticle

Lindroth, AM, Yoon, JP, McLean, CM, Dokshin, GA, Persson, JM, Herman, H, Pasini, D, Miró, X, Donohoe, ME, Lee, JT, Helin, K & Soloway, PD 2008, 'Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus', PLoS Genetics, vol. 4, no. 8, e1000145. https://doi.org/10.1371/journal.pgen.1000145
Lindroth AM, Yoon JP, McLean CM, Dokshin GA, Persson JM, Herman H et al. Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus. PLoS Genetics. 2008 Aug;4(8). e1000145. https://doi.org/10.1371/journal.pgen.1000145
Lindroth, Anders M. ; Yoon, Jung Park ; McLean, Chelsea M. ; Dokshin, Gregoriy A. ; Persson, Jenna M. ; Herman, Herry ; Pasini, Diego ; Miró, Xavier ; Donohoe, Mary E. ; Lee, Jeannie T. ; Helin, Kristian ; Soloway, Paul D. / Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus. In: PLoS Genetics. 2008 ; Vol. 4, No. 8.
@article{8a9198b6c64045378fc60782d40b79eb,
title = "Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus",
abstract = "At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.",
author = "Lindroth, {Anders M.} and Yoon, {Jung Park} and McLean, {Chelsea M.} and Dokshin, {Gregoriy A.} and Persson, {Jenna M.} and Herry Herman and Diego Pasini and Xavier Mir{\'o} and Donohoe, {Mary E.} and Lee, {Jeannie T.} and Kristian Helin and Soloway, {Paul D.}",
year = "2008",
month = "8",
doi = "10.1371/journal.pgen.1000145",
language = "English",
volume = "4",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus

AU - Lindroth, Anders M.

AU - Yoon, Jung Park

AU - McLean, Chelsea M.

AU - Dokshin, Gregoriy A.

AU - Persson, Jenna M.

AU - Herman, Herry

AU - Pasini, Diego

AU - Miró, Xavier

AU - Donohoe, Mary E.

AU - Lee, Jeannie T.

AU - Helin, Kristian

AU - Soloway, Paul D.

PY - 2008/8

Y1 - 2008/8

N2 - At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.

AB - At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.

UR - http://www.scopus.com/inward/record.url?scp=50849107031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50849107031&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1000145

DO - 10.1371/journal.pgen.1000145

M3 - Article

C2 - 18670629

AN - SCOPUS:50849107031

VL - 4

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 8

M1 - e1000145

ER -