Lecture on Epigenetics and Gene Regulation

Epigenetics is the study of changes in gene expression that do not involve alterations to the underlying DNA sequence. This includes mechanisms such as DNA methylation, histone modification, and non-coding RNA contributions, which all play critical roles in gene regulation and cellular differentiation. Understanding these mechanisms is essential for unpacking how environmental factors can influence gene expression and potentially lead to phenotypic variations.

Central Dogma of Molecular Biology

• DNA: Genetic code with a specific structure; base pair matching is critical.

  • Can be replicated (including post-translational modifications like methylation).

• Eukaryotic Transcription:

  • DNA is in the nucleus.

  • mRNA production.

  • Gene expression.

  • Focus on complexity of transcription.

• Translation:

  • Ribosome.

• Central dogma: DNA -> RNA -> Protein (transcription, translation).

  • RNA polymerase II is key (genes expressed by RNA polymerase two).

Gene Regulation and Chromatin Architecture

• Compacted DNA shuts down gene transcription.

• Mechanisms to open up (activate) or shut down genes.

• Dynamic process: packaged DNA -> opening up -> transcribing -> shutting down -> closing chromatin.

• Epigenetic markers regulate higher-order chromatin.

• Transcription regulation controls timing, location, and level of gene expression.

Gene Structure and Regulatory Elements

• Gene Definition: Region of DNA that encodes a protein or RNA.

• Two Main Regions: Coding Region and Regulatory Region.

  • Coding region contains protein-coding information (exons and introns).

  • Regulatory region is non-coding but controls gene expression.

• Gene Directionality: 5' end (upstream), 3' end (downstream).

• Regulatory region can span large amounts of DNA (tens or hundreds of kilobases).

• Regulation involves both activation and silencing.

Cis-Acting Regulatory Elements

• Cis-regulatory elements affect the same molecule of DNA.

• TSS Transcription Start Site: Where the Polymerase will bind to start producing RNA

• Proximal elements: Close to transcription start site.

• Distal elements: Further away.

Core Promoter Elements

• Core Promoter: Region where RNA polymerase is brought to and binds.

• TATA box: Core element with a conserved sequence TATA.

  • Functions as a landing site for TATA-binding protein.

  • Not present in all protein-coding genes.

Proximal Promoter Elements

• Modify how RNA polymerase is brought to promoter.

• Can influence stability and frequency of polymerase binding.

• Common elements: GC box (for constitutively expressed genes) and CAT box (for non-constitutive genes).

Distal Elements (Enhancers and Silencers)

• Can be kilobases away from the start of the gene, but can influence expression.

• Enhancers: Enhance gene expression; can be up to one megabase away.

• Silencers: Repress genes.

• Regulatory regions can also be downstream of a gene.