Chapter 18 Concept 18 1 Bacteria often respond to environmental change by regulating transcription Cells can regulation production of enzymes by feedback inhibition or by gene regulation The operon model controls Gene expression in bacteria Discovered by Francis Jacob and Jacques Operon The basic Concept a single on off switch positioned within the promoter A cluster of functionally related genes can be under coordinated control by The regulatory Switch is a segment of DNA called an operator usually An operon is the entire stretch of DNA that includes the operator the promoter and the genes that they control Repressor Protein that switches off the operon Prevents the gene transcription by binding to the operator and blocking RNA polymerase Regulatory gene produces the repressor Repressor is specific for each operon Co Repressor Molecule that cooperates with a repressor protein to switch an operon off E Coli can synthesize the amino acid tryptophan Repressible and Inducible operons operator shuts off transcription Repressible operon one that is usually on binding of a repressor to the The TRP operon is a repressible operon Repressible operons are in anabolic pathways Inducible operon usually off a molecule called an inducer inactivate the repressor and turns on transcription LAC operon is an inducible operon Inducible enzymes are in a catabolic pathway TRP operon on off the TRP operon Default is on and genes for tryptophan synthesis are transcribed while its Tryptophan is present it binds to the TRP repressor protein which turns TRP operon is off if tryptophan levels are high Lac operon Activated by presence of lactose Code for enzymes used in the hydrolysis of lactose Normally off lac repressor is active Inducer Inactivates the repressor to turn the lac operon on Concept 18 2 Eukaryotic gene expression is regulated at may stages Cell specialization multicellular organisms regulation of gene expression Differential Gene Expression Differential Gene Expression Differences between cell with the same genome Abnormalities in gene expression can lead to diseases including cancer Stages of gene expression 1 Transcription 2 Translation 3 Post Translation Chemical groups added to proteins a Add monosaccharide glycoproteins b Add fatty acid lipoprotein c Ad phosphate Causes rapid and reversible effect on protein function activate inactivate proteins Regulation of chromatin structure Genes in heterochromatin are not usually expressed Histone modifications lysine in histone tails transcription Histone Acetylation Acetyl groups are attached to positively charged Loosens chromatin structure there by promoting the initiation of Methylation Addition of methyl groups condenses chromatin Phosphorylation addition of phosphate group next to a methylated amino acid can loosen chromatin Histone Code Hypothesis Proposes that specific combinations of medication as well as the order in which they occur help determine chromatin configuration and influence transcription DNA methylation DNA methylation Addition of methyl groups to certain bases in DNA associated with reduced transcription in some species Can cause long term inactivation of genes in cellular differentiation Cytosine is methylated in Genomic Imprinting methylation regulates expression of either maternal or paternal alleles Epigenetic Inheritance Epigenetic Inheritance Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence Explains differences in twins Regulation of transcription Chromatin modifying enzymes provide initial control of gene expression by making a region of DNA either more or less able to bind to the transcription machinery Organization of a typical Eukaryotic Gene Control Elements segments of non coding DNA that serve as binding sites for transcription factors that help regulate transcription The Roles of transcription factors Transcription Factors Proteins that eukaryotic RNA polymerase require to assist in the initiation of transcription Essential for transcription of all protein coding genes In Eukaryotes high levels of transcription of particular genes depend on control elements interactions with high specific transcription factors Enhancers and Specific transcription factors Proximal control Elements are located close to the promoter Distal control Elements grouping of which are called Enhancers may be far away from a gene or even located in an intron Activator A protein that binds to an enhancer and stimulates transcription of a gene 2 Domains Binds to DNA Transport Bound activators facilitate a sequence of protein protein interactions that result in transcription of a given gene DNA bends to bring bound activators to the promoter region the bound activator interacts with the mediator proteins to help assemble and position the initiation complex on the promoter Some transcription factors function as repressors inhibiting expression of a particular gene by a variety of methods some bind to control elements to block activator binding Some activators and repressors act indirectly by influencing chromatin structure to promote or silence transcription Some activators recruit proteins that acetylate histones near Some repressors recruit proteins that deacetylate histones promoters RNA processing Alternative RNA splicing different mRNA molecules are produced from the same primary transcript depending on which RNA segments are treated as exons and which are treated as introns mRNA Degradation protein synthesis The life span of mRNA molecules in the cytoplasm is a key to determining Eukaryotic mRNA is much longer lived than prokaryotic mRNA Life span of mRNA resides in untranslated region UTR of the 3 end of mRNA Initiation of Translation The initiation of translation of selected mRNA s can be blocked by regulator proteins that bind to sequences or structures of mRNA s at the 5 UTR Alternatively translation of all mRNA s in a cell may be regulated simultaneously degrade them Protein Processing and Degradation Proteasomes giant protein complexes that bind protein molecules and Ubiquitin Proteins destined for proteasome Concept 18 3 Non coding RNA s play multiple roles in controlling gene expression Only small fraction of the non protein coding DNA consist of genes for RNA Non Coding RNA s ncRNA Significance amount of the genome may be transcribed into this type of RNA Regulate gene expression 1 mRNA translation 2 Chromatin configuration Effects on mRNA s by microRNAs and small interfering
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