Epigenetic mechanisms

• Epigenetic mechanisms
• MiRNAs are small non-coding RNAs that regulate gene expression at the posttranscriptional level by binding to mRNAs.
• Chromatin in Euchromatin State
• By the end of Lecture 12, students should be able to:

  • Describe epigenetic mechanisms for the control of gene expression
  • Define epigenetic inheritance
  • Define post-transcriptional control
  • Outline how microRNAs can block the production of a particular protein and specify how the mRNAs targeted by this mechanism can be destroyed
  • Summarize the role that RNA interference plays in cell defense
• Epigenetic control of gene expression:

  • Transcription factors and RNA polymerase can access regulatory regions and transcribe genes in euchromatin state
  • Transcription factors and RNA polymerase are unable to access regulatory regions and transcribe genes in heterochromatin state
• Epigenetic modifications:

  • Histone modification involves adding acetyl groups by histone acetyltransferases, leading to a more euchromatic chromatin state
  • Histone methylation involves adding methyl groups by histone methyltransferases, changing chromatin state
  • DNA methylation occurs on cytosine bases, generally turning off transcription by blocking proteins that attach to DNA
• Epigenetic modifications are heritable:

  • Epigenetic modifications can be passed down to progeny cells during cell division
  • Environmental factors like diet, stress, and exposure to toxins can influence epigenetic modifications
  • DNA methylation patterns can be inherited when a cell divides
  • Histone modifications may be inherited by daughter chromosomes
• Non-coding regulatory RNAs:

  • MicroRNAs direct the destruction of target mRNAs by forming an RNA-induced silencing complex (RISC)
  • Small interfering RNAs (siRNA) protect cells from infections and destroy complementary RNA molecules through RNA interference (RNAi)
• Histone Modification - Histones can be modified through acetylation, methylation, phosphorylation, ubiquitination, sumoylation, ADP ribosylation, etc.
• Acetylation is associated with transcriptionally active chromatin, while deacetylated histones are linked to repressed genes.
• Different combinations of modifications on histones result in different states of chromatin structure and function.
• Acetylation is associated with active transcription, while deacetylation is associated with repression.
• Methylation is associated with both activation and repression depending on the site.
• Phosphorylation is associated with regulation of transcription factor binding.
• Chromatin remodeling enzymes use ATP hydrolysis to move nucleosomes along DNA strands.
• The combination of specific modifications at particular sites within the genome determines gene expression levels.
• Chromatin remodeling enzymes play important roles in regulating gene expression by modifying histones or other components of nucleosomes.
• Adenosine triphosphate (ATP)-dependent chromatin remodelers use energy derived from ATP hydrolysis to alter the positioning of nucleosomes relative to DNA sequences.
• Phosphorylation of specific amino acid residues within histones can also affect their interactions with DNA and other proteins.