Transcriptional Control and Epigenetics

  • Introduction to Transcriptional Control

    • Reflection on previous discussions of epigenetics and its relevance in expression of genes, particularly through cell division.
    • Daughter cells replicate genetic material and modifications from parent cells.

  • Epigenetics Overview

    • Definition: Chemical modifications that affect gene expression without altering the DNA sequence itself.
    • Types of Modifications: Can occur through DNA or associated histones (proteins around which DNA is wound).
    • Example: Genomic imprinting, where specific genes are silenced in the formation of gametes (sperm or egg), leading to inheritance patterns.

  • Genomic Imprinting

    • Key point: Only certain genes undergo this phenomenon, not randomly.
    • Results in the inheritance of either active or silenced alleles, depending on parental contribution.

  • Modifying Gene Expression

    • Environmental influences suggested to impact epigenetic changes related to conditions such as autism.
    • Behavioral influences: Evidence suggests that an active lifestyle in older individuals may positively influence the gene expression of subsequent generations.

  • Historical Perspective

    • Reference to Lamarckian evolution: Earlier theories on how changes in individuals could be passed down vs. modern understanding of genetics.

  • Gene Expression and Modification

    • Differences between silencing genes (gene expression not active) and activating them (gene expression turned on).
    • The sequence of DNA remains unchanged; only expression levels are modified.

  • Chemical Modifications

    • Methylation of DNA (adding a methyl group to cytosine) often blocks transcription.
    • Histone modifications (like methylation or acetylation) can also affect gene expression, contributing to the so-called "histone code."

  • Chromatin Remodeling

    • Important for gene accessibility: Compressed chromatin typically silences genes, while open chromatin allows for transcription.
    • Experiment illustration: DNA susceptibility assays (use of DNase enzyme to cut DNA) reveal the structure of chromatin and its association with gene expression.

  • Experimental Design

    • Postulate whether the structure of chromatin affects accessibility to DNase and thereby gene expression.
    • Hypothesis: Less compacted DNA around expressed genes is more susceptible to DNase compared to more packed DNA.

  • Results Interpretation

    • Test both beta globin gene and ovalbumin gene for their susceptibility to DNase.
    • Observed results showed that beta globin is more susceptible to degradation by DNase, indicating less compacted chromatin around this gene compared to ovalbumin.

  • Significance of Findings

    • Correlation between accessible chromatin and active gene expression is evident, suggesting a powerful link between gene expression regulation and chromatin structure.
    • Explanation that genes not transcribed in certain cells (like insulin in brain cells) exhibit condensed chromatin, preventing expression.

  • Conclusion and Future Directions

    • Expanding upon transcriptional control mechanisms by understanding chromatin's role in gene expression.
    • Theoretical implications on how introns (non-coding regions) might influence gene expression despite not being translated into protein, prompting further experimental investigations.