PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos

Nature. 2012 Jun 3;486(7403):415-9. doi: 10.1038/nature11093.

Abstract

The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / metabolism*
  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • DNA Methylation
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism*
  • Embryonic Development
  • Female
  • Genomic Imprinting / genetics
  • Histones / chemistry*
  • Histones / metabolism*
  • Lysine / chemistry
  • Lysine / metabolism
  • Male
  • Methylation
  • Mice
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins / metabolism
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • Repressor Proteins / metabolism*
  • Spermatozoa / metabolism
  • ras-GRF1 / genetics

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Dppa3 protein, mouse
  • H19 long non-coding RNA
  • Histones
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Rasgrf1 protein, mouse
  • Repressor Proteins
  • ras-GRF1
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine
  • Tet3 protein, mouse
  • Lysine