Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Control of Gene Expression
Transcript
E. coli lac Operon Sequences that control the expression of the operon Control of Gene Expression Regulatory gene lacI lac operon Promoter Operator DNA lacZ lacA lacY Binds RNA Binds Lac polymerase repressor Transcription termination site Transcription initiation site Lac repressor Regulation of Inducible lac Operon !-Galactosidase Permease Transacetylase Inducible lac Operon b. Lactose present in medium a. Lactose absent from medium lac operon lac operon lacI DNA Promoter Operator lacZ Transcription blocked mRNA Lac repressor (active) RNA polymerase cannot bind to promoter lacY lacA When lactose is absent from the medium, the active Lac repressor binds to the operator of the lac operon, blocking transcription. lacI DNA mRNA Lac repressor (active) Promoter Operator RNA polymerase binds and transcribes operon Binding site Allolactose for inducer (inducer) lacZ lacY lacA Transcription occurs Inactive repressor Translation Lactose metabolism enzymes mRNA When lactose is present in the medium, some of it is converted to the inducer allolactose. Allolactose binds to the Lac repressor, inactivating it so that it cannot bind to the operator. This allows RNA polymerase to bind to the promoter, and transcription of the lac operon occurs. Translation of the mRNA produces the three lactose metabolism enzymes. Repressable trp Operon Regulation of the repressable trp Operon a. Tryptophan absent from medium b. Tryptophan present in medium Regulatory RNA polymerase binds and transcribes operon gene trpR DNA trp operon trpD Promoter Operator trpE trpC trp operon trpB trpA DNA Transcription occurs mRNA Trp repressor (inactive) trpR Translation Tryptophan biosynthesis enzymes mRNA When tryptophan is absent from the medium, the Trp repressor is inactive in binding to the operator and transcription proceeds. trpD Promoter Operator trpE trpC trpB Transcription blocked When tryptophan is present in the medium, the amino acid binds to, and activates, the Trp repressor. The active repressor binds to the operator and blocks transcription. mRNA Trp repressor (inactive) RNA polymerase cannot bind to promoter Tryptophanbinding site Tryptophan (corepressor) Trp repressor (active) Cytoplasm Chromatin DNA Pre-mRNA Mature RNAs Mature RNAs Initiation of protein synthesis New polypeptide chains Finished proteins Protein breakdown Chromatin Remodeling Nucleus Transcriptional regulation • Chromatin remodeling to make genes accessible for transcription • Regulation of transcription initiation Posttranscriptional regulation • Variations in pre-mRNA processing • Removal of masking proteins • Variations in rate of mRNA breakdown •RNA interference Determines which genes are translated Translational regulation • Variations in rate of initiation of protein synthesis Posttranslational regulation • variations in rate of protein processing • Removal of masking segments • Varieties in rate of protein breakdown Regulatory sequence Promoter Nucleosomes Gene Determines types and availability of mRNAs to ribosomes Promoter not accessible to proteins for transcription initiation Activator Ribosome trpA Chromatin remodeling exposes promoter Determines rate at which proteins are made Remodeling complex Determines availability of finished proteins Promoter Gene Promoter now accessible to proteins for transcription initiation Organization of Eukaryotic Gene Transcription Complex on the Promoter Initial general transcription factor Enhancer Promoter proximal region Promoter transcription factor recognizes and binds to the TATA box of a proteincoding gene’s promoter. DNA TATA box Transcription unit of gene Exon Intron Exon Intron Exon Promoter TATA 5' UTR proximal box elements (regulatory sequences) Site where transcription starts Promoter DNA Regulatory sequences 1 The first general 3' UTR Additional general transcription factors RNA polymerase DNA Transcription begins 2 Additional general transcription factors and then RNA polymerase add to the complex, and then transcription begins. Transcription complex Interactions Between Activators Combinatorial Gene Regulation Coactivator (multiprotein complex) A unique combination of activators controls gene A. Transcription initiation site Activators Activators Gene Enhancer Promoter Promoter proximal region Interaction between activators at the enhancer, coactivator, and proteins at the promoter and promoter proximal region DNA loop Gene Maximal transcription Activators 2 5 7 8 DNA Enhancer regulatory sequences 2 5 7 8 Transcription Gene A Enhancer Gene A, controlled by activators 2, 5, 7, and 8 binding to regulatory sequences in its enhancer Steroid hormone Combinatorial Gene Regulation Steroid hormone receptor A different combination of activators controls gene B. DNA Activators DNA Enhancer regulatory sequences 1 5 8 11 5 8 Enhancer 11 RNA polymerase Transcription Steroid hormone Gene controlled response element by the steroid hormone Pre-mRNA Transcription Gene B 1 Hormone bound to receptor Gene B, controlled by activators 1, 5, 8, and 11 binding to regulatory sequences in its enhancer DNA methylation silences genes mRNA mRNA + ribosomes Protein Histone acetylation activates genes !The hemoglobin genes for instance are highly methylated and thus silenced in most vertebrate body cells except red blood cells. !DNA methylation sometimes silences large blocks of genes or even whole chromosomes like one of the X chromosome in female mammals (Barr bodies) !DNA Methylation underlies genomic imprinting in which either the paternal or maternal allele of a particular gene is silenced. The DNA around acetylated histones is less tightly wrapped around the histones in the nucleosome and thus more accessible to DNA binding proteins including transcription factors and RNA polymerase. siRNA Dicer Precursor RNA folds into stem-loop miRNA precursor Protein Degradation Dicer Double-stranded RNA miRNA gene Other proteins bind and degrade one RNA strand Nucleus Cytoplasm Degradation of mRNA miRNA binds to complementary target mRNA Inhibition of translation Stepped Art Development of Colorectal Cancer Colon Normal colon epithelial cells Loss of tumorsuppressor gene p53 Activation of ras oncogene Loss of tumorsuppressor Colon wall gene APC (or other) Small benign growth (polyp) Loss of tumorsuppressor gene DCC Additional mutations Larger benign growth (adenoma) Malignant tumor (carcinoma)
