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 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 Single transcript gives rise to 2 or more mature mRNAs encode different polypeptides with shared domains tissue and developmentally specific References This text is based on notes very generously donated by Paul Doerder, Ph.D., of the Cleveland State University.