Epigenetics, Gene Regulation and Disease - Module Notes

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Gene Regulation

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

• Eukaryotic genes are modulated independently through multiple levels of regulation.

• Regulatory elements include specific DNA sequences and proteins that bind to those sequences.

Cis-Regulatory Elements (CREs)

• Specific sequences in the regulatory region that influence expression of nearby genes.

• One gene is typically controlled by multiple CREs at different distances.

Core Promoter

• Essential for assembly of RNA polymerase II machinery.

• Contains elements like:

  • TATA box: Located ~25bp upstream of TSS, consensus sequence TATAAA.

  • Initiator.

  • Downstream core promoter elements (DPE).

Proximal Promoter Elements

• Cooperate with core promoter to regulate transcription.

• Located ~250bp upstream of TSS.

• Contains binding sites for trans-acting regulatory elements.

  • GC box: ~110bps upstream, consensus sequence GGGCGG.

  • CAAT box: ~60-100bps upstream, for non-constitutively expressed genes.

Distal Promoter Elements

• Located several Kbp away from TSS.

• Includes:

  • Enhancers: Increase activity of core promoter, can be up to 1Mbp away.

  • Silencers: Reduce or prevent gene transcription, mostly upstream of core promoter.