Lecture on DNA Methylation and Gene Expression

Key Concepts

DNA Sequence and Gene Expression

• All cells contain the same DNA sequence.
• Different cells express only certain genes.

Epigenetic Modifications

• Epigenetic modifications alter gene expression without changing the DNA sequence.
• DNA Methylation is a key epigenetic modification.
  • Involves tagging DNA with chemical groups.
  • Associated with gene silencing.
  • Crucial for maintaining cell types.
  • Altered and disrupted in cancer.

DNA Methyltransferases (DNMTs)

• Enzymes responsible for DNA methylation.
• Three major types: DNMT1, DNMT3A, DNMT3B.
  • DNMT3A & DNMT3B: Responsible for de novo methylation in embryonic cells.
  • DNMT1: Responsible for maintenance methylation during cell division.

Mechanism of DNMTs

• DNA is wrapped around histone octamers (nucleosomes).
• De novo methylation by DNMT3A & DNMT3B in early embryonic cells for differentiation.
• Maintenance methylation by DNMT1 to retain cell type specific methylation patterns.

CpG Sites and Islands

• CpG sites: Cytosine-Guanine sequences in DNA.
• CpG islands: Regions with high frequency of CpG sites.
• Most CpG sites are methylated in adult cells, except in promoter CpG islands.

DNA Methylation Process

• Methylation involves addition of a methyl group from SAM to cytosine, forming 5-methylcytosine.
  • DNMT enzymes flip the cytosine out of the DNA strand for methylation.
  • Methylated cytosine is flipped back into the strand.

TET Enzymes

• Responsible for DNA demethylation.
• Convert 5-methylcytosine to 5-hydroxymethylcytosine, then back to cytosine.
• Regulate methylation patterns tightly in normal cells.

DNA Methylation in Cancer

• Methylation and demethylation balance is disrupted.
• Hypermethylation: Increased methylation in promoter CpG islands, often silencing tumor suppressor genes.
• Hypomethylation: Reduced methylation across the genome.
• Both hypermethylation and hypomethylation are common in all human tumors.
• Alterations in methylation patterns aid in cancer detection.