Genes and Phenotypic Expression: Cellular Differentiation and Epigenetics

Cellular Differentiation

• Different cell types in the body have varying structures suited to their specific functions.
  • Examples: neurons, red blood cells, smooth muscle cells, and white blood cells.
• At fertilization, stem cells are undifferentiated with the potential to become any cell type.
• Each cell contains identical DNA; specialization depends on which genes are activated or deactivated.
• Gene activation depends on cell position in the embryo and intended function.
• Specialized cells form tissues. Activation of genes enables cells to differentiate.
  • Muscle cells have a cytoskeleton made of proteins which allows it to contract. Synthesis of proteins is directed by activation of particular genes on chromosomes.
  • Once differentiated, cells generally cannot revert to other types.

Epigenetics and Gene Silencing

• Epigenetic factors, changes during a parent cell's lifetime, are passed to daughter cells via cell division.
  • Daughter cells inherit the same silenced or switched-on genes.

Methylation

• Within multicellular organisms, different cell types contain the same genetic material but have different structures and functions.
• Genes can be 'locked off' via the addition of a methyl group (CH3) to cytosine nucleotides.
  • CH_3: represents a methyl group, a carbon atom bonded to three hydrogen atoms.
  • Adenine may also be methylated, particularly in prokaryotes.
• Epigenetics can explain phenotypic differences in identical twins or clones, despite initially identical DNA.
• Environmental factors may influence gene switching, potentially impacting conditions like type one diabetes.

Histone Modification

• Changes in DNA methylation and histone modification can alter gene expression.
• Histone modification involves chemical changes to histone proteins, including:
  • Methylation
  • Acetylation
  • Phosphorylation
  • Ubiquitination
• In eukaryotes, DNA wraps around histone proteins, influencing chromatin structure and gene expression.
• Methylation of cytosine nucleotides or histone proteins can block RNA polymerase from attaching, preventing transcription.
• Methylation patterns are usually retained during cell division, passing the silenced state to daughter cells.
• Epigenetics refers to heritable changes in gene expression.
• Limited evidence suggests lifestyle changes directly alter DNA for offspring inheritance; such changes are considered rare and not a significant driving force in evolution.

Epigenetics and Disease

• Cancer can result from uncontrolled cell division if tumor suppressor genes become methylated.
  • Methylation prevents transcription, disabling control over cell division and leading to tumor formation.
• Epigenetic changes that turn off DNA repair genes increase the chance of cancer.
• Excessive cytosine methylation is linked to human diseases, such as:
  • Fragile X syndrome
  • Prader-Willi syndrome
  • Angelman syndrome

Fragile X Syndrome

• Fragile X syndrome results from methylation of cytosine in CGG repeats in the FMR1 gene.
  • This methylation prevents production of a protein needed for normal protein development.
  • Occurs in individuals with more than 200 CGG repeats; typical range is 6-44 repeats.
• Symptoms include chromosome instability and intellectual disability.

Key Takeaways

• Phenotypic expression depends on factors controlling transcription and translation.
• Changes in DNA methylation and histone modification can alter gene expression, affecting phenotypic expression.
• Epigenetic modifications in genes controlling cell division can lead to cancer due to unchecked cell division.