Epigenetics vs Genetics

• Study notes based on Week 2 Study Guide Questions:

Epigenetics vs. Genetics

• Epigenetics is the study of heritable changes in gene expression that do not involve alterations to the DNA sequence itself.
• Genetics focuses on the DNA sequence and its variations (mutations) as the primary source of heritable traits.
• Epigenetics can influence whether genes are turned on or off, without changing the underlying genetic code.

Coining of "Epigenetics"

• Conrad Waddington coined the term "epigenetics."
• It was coined in 1942.

Core Mechanisms of Epigenetic Inheritance

• DNA methylation: The addition of a methyl group to a DNA base, typically cytosine, which can repress gene transcription.
• Histone modification: Chemical modifications to histone proteins (e.g., acetylation, methylation, phosphorylation) that alter chromatin structure and affect gene expression.
• Non-coding RNA: Molecules like microRNAs (miRNAs) that regulate gene expression by targeting mRNA for degradation or translational repression.

Environmental Influence on Epigenetic Changes

• Environmental factors like diet, exposure to toxins, and stress can induce epigenetic changes
• These changes can alter gene expression patterns.
• Example: Exposure to famine during pregnancy can cause epigenetic modifications in the offspring
• This leads to a higher risk of metabolic disorders.

Role of RNA in Epigenetics

• RNA plays a significant role in epigenetics via non-coding RNAs.
• siRNAs, miRNAs, and lncRNAs are involved in gene expression.
• These can guide DNA methylation, modify histones, or directly interact with mRNA.

Histone Acetylation

• Histone acetylation is the process where acetyl groups are added to histone proteins.
• This is typically associated with increased gene expression.
• Acetylation loosens the chromatin structure, making DNA more accessible to transcription factors.

Chromatin

• Chromatin is the complex of DNA and proteins (histones) that forms chromosomes within the nucleus of eukaryotic cells.
• Chromatin structure (open/closed) affects gene expression.
• Open chromatin (euchromatin) allows gene transcription.
• Closed chromatin (heterochromatin) represses gene transcription.

Epigenetic Changes and Cancer Development

• Epigenetic changes can contribute to cancer development by altering the expression of genes involved in cell growth, DNA repair, and apoptosis.
• Aberrant DNA methylation and histone modifications can lead to the activation of oncogenes or the silencing of tumor suppressor genes.

Reversibility of Epigenetic Changes in Disease Treatment

• The reversibility of epigenetic changes makes them attractive targets for disease treatment.
• Epigenetic drugs like DNA methyltransferase inhibitors (DNMTis) and histone deacetylase inhibitors (HDACis) can reverse aberrant epigenetic marks.
• This affects cancer development.

Epigenetics and Child Development

• Epigenetics plays a crucial role in child development
• Early life experiences (e.g., nutrition, stress, parental care) can induce epigenetic changes that affect brain development and behavior.
• These changes can have long-lasting effects on health and well-being.

Epigenetic Inheritance

• Epigenetic inheritance is the transmission of epigenetic marks from one generation to the next.
• Example: transgenerational inheritance of stress-induced behaviors through epigenetic modifications in germ cells.

Types of Histone Modifications

• Different types of histone modifications include:
  • Acetylation (associated with increased gene expression)
  • Methylation (can either activate or repress gene expression, depending on the specific residue modified)
  • Phosphorylation (involved in various cellular processes, including gene expression)
  • Each modification influences gene expression by altering chromatin structure and/or by recruiting specific regulatory proteins.