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Unformatted text preview: 204-325 1 Summary of the Last lecture The RNA coding sequence (structure genes), operator and promoter are parts of an operon. A repressor protein (such as lacI or trp-trpR) can bind to the operator to block the transcription of an operon. An activator protein (such as CAP-cAMP) can bind in promoter to increase the transcription. mRNA secondary structure could also be used to control the termination of the transcription. This is known as attenuation. 2 Today's Topics 1. Genomic Equivalence 2. Transcriptional Regulation 3. Posttranscriptional Regulation 3 Topic 1 Genomic Equivalence
4 Cloning of a Carrot from a Cell (1950s) 5 Evidence for Genomic Equivalence: Cloning a Frog (1975) 6 Sheep Cloning Experiment (1997) 7 Exception: Somatic Recombination in the Production of IgG 350 Translation Deleted from the Genome of a Subset of B Cells 8 Gene Expression Controls in Eukaryotes
Transcriptional Regulation Posttranscriptional Regulation Translational Regulation Posttranslational Regulation
9 Topic 2 Transcriptional Regulation
10 Rare Eukaryotic Operons: Polygenic to Monogenic mRNA Removed Trans-Splicing 15% genes in C. elegans are in operons 11 Regulation of Gene Transcription 12 Regulatory DNA Sequence of mRNA Gene TATA
(~-25) Regulatory DNA Basal Element Promoter Silencer Enhancer
(-0) Proximal Element (-50~-200) Transcriptional Regulation Through Coactivators 14 Coactivators are also Known as Mediators 15 Most Genes are Controlled by Combinatorial Regulation 16 Major Classes of DNA-binding Proteins c) 17 Galactose Metabolizing Pathway of Yeast 18 Galactose (GAL) Utilization Gene Regulation in Yeast UASG=Upstream Activating Sequence for Gal4 19 Activation of the GAL Gene Transcription 20 Polypeptide Hormones and Steroid Hormones 21 Structures of Some Mammalian Steroid Hormones 22 Action of Steroid Hormone Glucocorticoid HBD=Hormone Binding Domain AD=Activation Domain BD=DNA-binding Domain 23 Animation 1: Gene Regulation by Glucocorticoid 24 Chromatin Remodeling is Part of Transcription Regulation 25 Gene Silencing by Histone Deacetylation Silenced , a histone deacetylase Sir=Silent Information Regulation Rap=Repressor-Activator Protein 26 Many Histone Modifications are Known M = methylation A = acetylation P = phosphorylation 27 Temporal Regulation of Gene Expression 28 Topic 3 Posttranscriptional Regulation 29 Alternative Polyadenylation and Alternative Splicing Protein Isoforms: one gene many proteins
30 Many Possibilities for Alternative Splicing 31 Animation 2: Posttranscriptional Regulation of Calcitonin Gene 32 Translation Control by Specific RNA-Binding Proteins IRE=Ion Response Element IRE-BP=IRE Binding Protein
33 RNA Stability Regulation Deadenylation dependent Deadenylation independent
34 Protein Stability Control: N End Rule N End Residue Yeast (minutes) After the initial N terminal fMet (E.coli) or Met (yeast) is removed by Met-aminopeptidases 35 Gene Regulation by RNA: RNAi (RNA Interference)
siRNA=Short Interfering RNA (21-23 nt) RISC=RNA-induced Silencing Complex 36 Gene Regulation by RNA: micro RNA RISC RISC=RNA-induced Silencing Complex
37 Summary During the development of multicellular eukaryotes, each specialized cells still contains the entire genome, although only part of it is expressed in any given cell at certain time. Gene expression is controlled by transcriptional regulation and posttranscriptional regulation in eukaryotes. Transcriptional activator proteins bind enhancer DNA sequences and work in combinatorial way to initiate transcription. Chromatin structure and histone modifications also regulate transcription. Posttranscriptional regulation also contributes to gene expression: RNA processing, RNA transport, RNA stability, translation, and protein stability. RNA interference and micro RNA are newly discovered mechanisms for regulating RNA stability and translation.
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