Proteomics

Dataset Information

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Complete loss of H3K9 methylation dissolves mouse heterochromatin organization


ABSTRACT: Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all 6 SET domain methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEFs no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is the first analysis of H3K9 methylation deficient mammalian chromatin and reveals a crucial function for H3K9 methylation in protecting heterochromatin organization and genome integrity.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Gerhard Mittler  

LAB HEAD: Gerhard Mittler

PROVIDER: PXD018175 | Pride | 2021-05-27

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Tmont_wedgeAtoH_gbA1_01.mgf-pride.xml Mgf
Tmont_wedgeAtoH_gbA1_01.raw Raw
Tmont_wedgeAtoH_gbA1_02.mgf-pride.xml Mgf
Tmont_wedgeAtoH_gbA1_02.raw Raw
Tmont_wedgeAtoH_gbA2_01.mgf-pride.xml Mgf
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Publications


Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six  ...[more]

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