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PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
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PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
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Journal Article
PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
2012
Overview
The binding of PGC7 to maternal chromatin, which is important for methylation maintenance during embryogenesis, is shown to be dependent on a particular histone modification, H3K9me2.
Protecting against DNA demethylation
During early embryogenesis, the paternal and maternal genomes undergo loss of the DNA modification 5-methylcytosine (5mC), but with different time courses. The maternal factor PGC7 is thought to be involved in protecting the maternal genome from demethylation. Here, the association of PGC7 with maternal chromatin is shown to be dependent on a particular histone modification, dimethylated histone H3 lysine 9 (H3K9me2). PGC7 binding can inhibit the binding of Tet3, an enzyme that converts 5mC into 5-hydroxymethylcytosine (5hmC).
The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation
1
. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes
2
,
3
. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment
4
,
5
,
6
,
7
. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome
8
,
9
. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Analysis
/ Animals
/ Biological and medical sciences
/ Cytosine - analogs & derivatives
/ DNA
/ DNA-Binding Proteins - metabolism
/ Embryo, Mammalian - embryology
/ Embryo, Mammalian - metabolism
/ Embryos
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Genomes
/ Genomic Imprinting - genetics
/ Genomics
/ Humanities and Social Sciences
/ letter
/ Male
/ Mice
/ Molecular and cellular biology
/ Peptides
/ Protein Binding - drug effects
/ Proto-Oncogene Proteins - metabolism
/ Repressor Proteins - metabolism
/ RNA, Untranslated - genetics
/ Science
/ Sperm
/ Transcription. Transcription factor. Splicing. Rna processing
