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PROKARYOTIC GENE REGULATION Cell must be able to respond to changes in environment OPERON model Related genes grouped together with single “on-off” switch called an OPERATOR PROMOTOR- region where RNA polymerase binds to start transcription REGULATORY GENE farther away makes REPRESSOR that binds to operator to control binding of RNA polymerase INDUCIBLE OPERON- Example: Lactose (lac) operon Operon is TURNED OFF REPRESSOR is in ACTIVE FORM unless INDUCER (lactose) is present – usually functions in catabolic pathways to digest nutrients into simpler – cell avoids making proteins that have nothing to do – cell allocates resources to other uses * * * * * * * * * * * * * REPRESSIBLE OPERON- Example: Tryptophan (trp) operon Operon is TURNED ON REPRESSOR is in INACTIVE FORM unless COREPRESSOR (tryptophan) is present – usually functions in anabolic pathways synthesizing end products – when end product is present in excess, cell allocates resources to other uses * * EUKARYOTIC DNA STRUCTURE LEVELS OF DNA PACKING REGULATE GENE EXPRESSION DNA packaged in chromatin fibers- regulates access to DNA by RNA polymerase NUCLEOSOMES- made of DNA wrapped around 8 HISTONE proteins HETEROCHROMATIN-tightly packed/no transcription EUCHROMATIN- loosely packed/transcription Acetylation (-COCH3) of histones unwraps DNA NUCLEOSOMES→ FIBERS→LOOPED DOMAINS→ CHROMOSOMES EPIGENETIC INHERITANCE – inheritance not carried by nucleotide sequence Genomic imprinting-methylation of DNA bases inactivates genes EX: Angelman’s (maternal) & Prader Willi (paternal) syndromes All cells have ALL GENESCell specialization (differentiation)= result of different cells turning on/off different genes (ACTIVATORS/REPRESSORS) POST TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION ALTERNATIVE RNA PROCESSING- different mRNA’s can be made by editing same transcript depending on which parts are treated as introns/exons mRNA DEGRADATION- siRNA’s (small interfering)- bind to mRNA and degrade it INITIATION OF TRANSLATION-regulatory proteins can prevent attachment of ribosomes PROTEIN PROCESSING/DEGRADATION-control activation and degradation of proteins UBIQUITIN protein- tags proteins for destruction PROTEASOMES-recognize ubiquitin tags and digest tagged proteins Genes= only ~3% of human genome protein-coding sequences (1%) non-protein coding genes (2%) -tRNA’s, rRNA’s, siRNA’s Most of DNA (97%) does not code for protein regulatory sequences- promoters, enhancers, terminators “junk” DNA o Introns o repetitive DNA (centromeres, telomeres, tandem & interspersed repeats) Ex: Fragile X syndrome – CGG repeats in promoter region on X chromosome most common cause of inherited mental retardation Ex: Huntington’s- CAG repeats produces mutant Huntingtin protein that causes neurological damage o transposons – 1st discovered by Barbara McClintock in corn segments of DNA that move within genome; function unknown Ex: Alu in humans (10% of human genome) o retrotransposons- segments move with help of RNA intermediates and reverse transcriptase coded for by retrotransposon (may be source of retroviruses) Many genes exist in MULTIGENE FAMILIESCan be collections of identical or similar genes EX: genes for rRNA subunits Can be differentEX: HEMOGLOBIN-multiple chains coded for on different chromosomes; used at different times (Fetal hemoglobin is different from adult hemoglobin) PSEUDOGENES-nonfunctional sequences similar to functional genes Can be used to determine evolutionary relationships EX: Humans and other primates have nonfunctional pseudogene for vitamin C production 70% of the almost 100 different odor receptor genes are nonfunctional in humans HOMEOTIC GENES- control overall body plan in plants and animals by regulating development 1st discovered as fruit fly mutants with body parts in wrong places Highly conserved (few mutational changes) Called HOX genes in animals EUKARYOTIC GENE REGULATION No OPERONS-individual genes PROMOTOER still binds RNA POLYMERASE Regulatory sequences near or far from gene control its expression TATA BOXES within PROMOTER region help RNA polymerase attach ENHANCER REGION upstream bends; ACTIVATORS help RNA Polymerase attach Numerous other proteins TRANSCRIPTION FACTORS/MEDIATORS also involved SPECIFIC TRANSCRIPTION FACTORS (activators and repressors) in each kind of cell determine which genes are expressed (Ex: ALBUMIN made in liver cell; CRYSTALLIN made in eye lens cell)