General Biology/Genetics/Gene Regulation
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- Not all genes are expressed in a cell
- Gene expression can be turned on and off
- Multiple levels of regulation gene function
- Transcription initiation
- State of chromatin
- Transcription factors
- Post-transcriptional
- mRNA processing
- mRNA half-life
- Translational
- Post-translational
- Protein modification
Transcriptional control
edit- State of chromatin
- Euchromatin: transcriptionally active
- Heterochromatin: transcriptionally inactive
- Chemical modification of histones
- Methylation of bases
- Transcription factors
- Bind to DNA at promoter or other regulatory sites (enhancers)
- Recognize base sequence through major and minor grooves
- Recruit RNA polymerase
DNA grooves
editCategories of transcription factors in eukaryotes
- Helix-turn-helix
- Two small "-helices
- Fit into DNA groove
- Homeodomain
- Highly conserved helical domains
- ~60 amino acids
- Zinc finger motif
- Zn atom bound
- Leucine zipper
- dimer
Regulatory proteins
edit- Activity may depend upon allosteric binding of small molecules
- cAMP
- Co-repressors
- Inhibitors
- Binding to promoter region may “bend” DNA, making it accessible to other regulatory proteins
Lac operon of E. coli
edit- Single promoter region for cluster of genes
- Regulated and transcribed as a single unit
- Operons typical in prokaryotes
- Repressor: turns OFF gene expression
lac repressor
- Turns off transcription by blocking access by RNA polymerase
- repressor in activated by allosteric binding of lactose
Regulation in eukaryotes
- Both proximal (promoter) and distal (enhancer) to gene
- Typically transcription unit encodes a single polypeptide
- Promoter
- TATA box
- Other elements (regulatory sequences) may be present
- Enhancers
- Work upstream, downstream, close, far from gene
- Bend DNA
Alternative splicing
edit- Single transcript gives rise to 2 or more mature mRNAs
- encode different polypeptides with shared domains
- tissue and developmentally specific
References
editThis text is based on notes very generously donated by Paul Doerder, Ph.D., of the Cleveland State University.