Part 8: Gene Expression Regulation
Controlling Gene Activity
Gene regulation determines when, where, and how much of a gene product is made. This allows cells to respond to environmental changes, differentiate into specialized types, and maintain homeostasis. Regulation can occur at multiple levels.
The Lac Operon (Prokaryotic Model)
The lac operon in E. coli is a classic model of gene regulation discovered by Jacob and Monod (1961).
Components
- • lacZ, lacY, lacA (structural genes)
- • Promoter and Operator
- • lacI (repressor gene)
- • CAP binding site
Regulation
- • Negative: Repressor blocks transcription
- • Positive: CAP-cAMP activates
- • Induction by lactose (allolactose)
- • Catabolite repression by glucose
Eukaryotic Gene Regulation
Transcriptional Regulation
- Enhancers/Silencers: Cis-acting elements, can act at distance
- Transcription Factors: Activators and repressors (DNA-binding + activation domains)
- Chromatin Remodeling: HATs/HDACs modify histones, affect accessibility
- DNA Methylation: CpG islands, gene silencing
Post-transcriptional Regulation
- Alternative Splicing: Different exon combinations → protein isoforms
- mRNA Stability: AU-rich elements, poly(A) tail length
- miRNA/siRNA: Small RNAs target mRNA for degradation or block translation
Translational & Post-translational
- Translation initiation: eIF4E availability, mTOR pathway
- Protein modifications: Phosphorylation, ubiquitination, glycosylation
- Protein degradation: Ubiquitin-proteasome system
Epigenetics
Heritable changes in gene expression without DNA sequence changes
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DNA Methylation
5-methylcytosine at CpG sites
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Histone Modifications
Acetylation, methylation, phosphorylation
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Non-coding RNAs
lncRNAs, piRNAs, chromatin regulation