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Genes differentially expressed after DNA methyltransferase 1 (DNMT1) knockdown in the presence or absence of early osteoblast (OB) differentiation

ABSTRACT: Genes differentially expressed after DNA methyltransferase 1 (DNMT1) knockdown in the presence or absence of early osteoblast (OB) differentiation

PROVIDER: PRJNA745562 | ENA |

REPOSITORIES: ENA

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Genes differentially methylated after DNA methyltransferase 1 (DNMT1) knockdown in the presence or absence of early osteoblast (OB) differentiation [RRBS]

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Genes differentially expressed after DNA methyltransferase 1 (DNMT1) knockdown in the presence or absence of early osteoblast (OB) differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

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Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome

Project description:The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on DNMT1. Functional studies further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that is preferentially at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.

2023-07-26 | PXD043031 | Pride

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Project description:RNA-seq analysis was performed to identify early OB-regulating genes in C3H10T1/2 MSCs.

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