General Biology/Genetics/Gene Regulation


 * 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

 * 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
Categories 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

 * 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
lac repressor Regulation in eukaryotes
 * Single promoter region for cluster of genes
 * Regulated and transcribed as a single unit
 * Operons typical in prokaryotes
 * Repressor: turns OFF gene expression
 * Turns off transcription by blocking access by RNA polymerase
 * repressor in activated by allosteric binding of lactose
 * 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

 * Single transcript gives rise to 2 or more mature mRNAs
 * encode different polypeptides with shared domains
 * tissue and developmentally specific