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  • Writer's pictureDr Edin Hamzić

⚗️ What Is De Novo Methylation?

Updated: Jan 11

⚗️ What Is De Novo Methylation?

  • ⚠️DNA methylation is a form of DNA modification in mammals characterized by adding a methyl group to position C5 of the pyrimidine ring of cytosines, predominantly in CpG dinucleotides or so-called CpG islands.

  • ⚠️ DNA methylation is one of the epigenetic marks, and DNA methylation of gene promoters is generally linked with the promoter being inactivated or silenced. To illustrate, 80% of CpG dinucleotides in DNA are methylated, with introns, exons, satellite DNAs, and transposons [citation].

  • ℹ️ CpG islands (CGIs) are regions in the genome characterized by a high density of CpG dinucleotides (elsewhere, CpGs are under-represented in vertebrate genomes). The length of CGIs is usually between a few hundred and a few thousand base pairs. CpG islands can be detected in genome sequences using specific bioinformatics algorithms or biochemically using specific proteins with CG-binding domains.

CpG islands are associated with essential regulatory elements.
  • Epigenetic marks are molecular determinants characterized by the ability to regulate gene expression and genome function in general. This further leads to heritable changes in gene expression without DNA sequence being changed.

The key epigenetic marks are post-translational modifications of histone proteins and DNA methylation.
  • De novo DNA methylation is a process by which methyl groups are added to unmethylated DNA at specific CpG sites where this process is catalyzed by DNMT3A and DNMT3B.

  • DNMT3A and DNMT3B are members of the DNA methyltransferase 3 (DNMT3) family and, as mentioned above, are crucial in de novo methylation [citation].

  • In the usual physiological setup, DNA methylation is widely erased, and then cell-type-specific DNA methylation patterns are established via de novo methylation. These new DNA methylation patterns are established during gametogenesis and embryogenesis.

🌚 De novo Methylation During Gametogenesis

  • ℹ️ During gametogenesis, more specifically, during oogenesis and spermatogenesis, de novo DNA methylation establishes oocyte- and sperm-specific DNA methylation patterns as those are eliminated in primordial germ cells (PGCs).

🌚 De novo Methylation During Embryogenesis

  • ℹ️ During post-implantation embryogenesis, de novo DNA methylation establishes DNA methylation patterns specific to each cell type after they are erased in preimplantation embryos.

  • In most differentiated cells, de novo DNA methylation is generally not desirable because once a DNA methylation pattern is established, it is crucial to precisely maintain it to keep the appropriate functions of each cell type.


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