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Gene Expression Open to Chapter 18 Dilemma • All the DNA in an organism’s cells is basically the same. • We have many of the same genes as a fruit fly (abt 60%). • What accounts for the differentiation in the cells? …Which genes are expressed. Regulation of Gene Expression • Regulation can occur at many levels in the DNA RNA PROTEIN – – – – Transcription Post-Transcription Translation Final Folding and Refolding of Proteins Overview • Prokaryotes have operons • Eukaryotes – – – – Regulatory sequences Selective transcription Homeobox Genes (HOX) Epigenome PROKARYOTE OPERON – Promotor- Where RNA polymerase attaches – Operator- switch that turns on or off. If repressor attaches, it is “off”. Transcription is disabled. – Gene – Examples: • Lac Operon- If Lactose is present, repressor inactive, gene turned on. • Trp Operon - If Tryptophan is present, repressor active, gene turned off. Figure 18.3b-1 DNA mRNA Protein Active repressor Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off Lac and Trp Operons • No matter which type of operon, when the repressor is active, the gene is switched___. • When lactose is present, the gene is switched _____ • When tryptophan is present, the gene is switched ______ Lac and Trp Operons • No matter which type of operon, when the repressor is active, the gene is switched off. • When lactose is present, the lac gene is switched on • When tryptophan is present, the trp gene is switched off What would happen if the repressor of an operon were mutated so that it could not bind to the operator? a) irreversible binding of the repressor to the promotor. b) reduced transcription of the operon’s genes c) continuous transcription of the operon’s genes EUKARYOTE REGULATORY SEQUENCES • Proteins (transcription factors) can bind to enhancer sequences on gene. Depending upon cellular conditions, this may enable gene to turn on (promote) or off (repress). Eukaryotes have multiple switches. – Induction- If proteins from neighboring cells are present, gene may turn on (ex: retina) – Hormones and other molecules may attach to enhancer sequence to turn on genes. Signal NUCLEUS Chromatin PAGE 356 Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Cap Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein processing, such as cleavage and chemical modification Degradation of protein Active protein Transport to cellular destination Cellular function (such as enzymatic activity, structural support) EPIGENOME • Environmental effects can impact gene expression. • Histone Acetylation- Adding acetyl group to histone proteins makes DNA more accessible, promoting transcription • Methylation seems to prevent genes from loosening from histones, repressing transcription. – Twins can have different diseases, and their gene expression becomes more divergent as they age. HOMEOBOX GENES • HOX genes (Homeotic genes) – Master control genes • Segmented organisms have HOX genes associated with genes for body parts. For example, since the same genes form antenna and leg, the structure that forms depends upon its HOX master control gene. Normal Head Mutant Head Transcriptional control • Name an epigenetic factor that in represses transcription. • Name an epigenetic factor that promotes transcription. • The reason that the same gene can code for either an antenna or a leg is that this gene is controlled by ______ SELECTIVE TRANSCRIPTION • During transcription, intervening sequences of mRNA are removed (introns). • Exons are spliced together. – Males and females have the same set of genes, the fact that they are spliced differently accounts for the difference in gender. – Splicing and DNA rearrangement account for millions of different antibodies from the same genes. Post transcriptional Modification RNAi • Interference RNA- RNAi • Regulates gene expression at transcription level, by attaching to complementary mRNA • Often inhibits or silences. • Forms may be called microRNA, or siRNA • See Video RNAi on Teachers Domain Figure 18.15 Hairpin Hydrogen bond miRNA Dicer 5 3 (a) Primary miRNA transcript miRNA miRNAprotein complex mRNA degraded Translation blocked (b) Generation and function of miRNAs Figure 18.25 Cancer is a multistep process -Mutations of tumor suppressor - Mutation of proto-oncogene Colon 1 Loss of tumorsuppressor gene APC (or other) Colon wall Normal colon epithelial cells 2 Activation of ras oncogene 4 Loss of tumorsuppressor gene p53 3 Loss 5 Additional mutations of tumorSmall benign suppressor Larger Malignant growth tumor gene DCC benign growth (polyp) (adenoma) (carcinoma) • See HMMI Click and Learn Genetic Switches • http://www.hhmi.org/biointeractive/geneswitch • See Controlling Protein Synthesis AP Boardworks, Slide 4-7 Muscle cells differ from nerve cells mainly because they a) express different genes b) contain different genes c) have different chromosomes