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Meet Genetic master chefs [Trans fac

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Generic master chefsʼ recipes for life
• Fruit fly/nematode worm (well-mapped mlc genetics): • Research in gene expression progressing at a hectic pace • (Mammals = early days) • [hope human genome project --> mlc genetics of mammals --> assult on trans fac]
--------------2nd p. ----------------

• Cancer --> turned on (uncontrolled) cell growth • HIV --> own trans facs --> take over • CVD(partly)- harmful turned on • --> research ctrl gene expression e.g. antiviral to inactivate trans fac

Gene Ctrl
• Gene therapy (healthy genes) + Trans fac to ctrl expression --> overide effects of damaged genes • Current: Understanding basic Sci of trans fac • (“supposed to be enormously scarce” [referring to older studies on bacteria] ) • Current estimate: 1000 < x < 10,000 / 100,000 (total no. of genes) • conc. = up to 20,000 mlc / cell • Collaborate --> ∞ combo ---> why genes can be “interpreted” in so many ways • 1960s- transcription, translation • RNA polymerase bind to “promoter”
• **[region of gene which protein binds causing assembling of mRNA]

• Postulate: RNA polymerase regulated by special protein subunits (“sigma factors”) • join before transcription • 1980s- proteins help RNA polymerase & activate specific genes • SP1 in human cells- Tijan • TFIIIA in frogsʼ eggs- Roeder, Rockefeller ------------3rd p. -----------• Now: discovered +100 trans fac in yeast, mammals w/ similar functions • Defining charac • “DNA-binding domains”- recognise specific sequence, dock into grove btw 2 nucleotides • Shapes- X-ray crystallography, NMR • Similar shapes --> families: leucine zippers, helix-loop-helix, Zn fingers • Leucine zipper- example of how trans facs can collaborate (---> ++combo) • Most studied- “fos” and “jun” --> cell division • implicated to cancer (∴ 2 = full zip) • each = ½zip • teeth = string of leucine amino (3 combo) • 3 shapes of teeth from 3 combo- fos/fos jun/jun fos/jun --> 3 diff. pathways • ∴ Understanding “activation domain” (part of mlc where trans facs interact) is as important as DNA-binding sequence

Activators and Repressors
• Overall shape is the most important • Repressor [1990s] discovered protein in bacteriophages • preventing RNA poly moving along it • Blocking construction of DNA-binding complex • Interfering w/ binding to DNA • **“duke it out” = fight it out

more complex software” • (1980s) Diverse species (Corn-yeast-humans) have similar stretches of DNA. The expression of a gene depends upon the parent who passed on the gene. gene expressed from the allele given by the other parent] • Some help chemical communications btw complex of trans facs.from head to tail (referring to chromosome) .g. RNA poly and DNA • Up to 60 proteins working together to turn on a single gene • Donʼt need to understand mech of all [diff.g. -------------4th p.g. pathways resulting the same thing like inflammation] • [Medical app. “homeoboxes” • (180 base-pairs coding for DNA-binding domains) • Found in genes that ctrl construction of basic body plan of fruit flies • (Now know) Genes that contain them encode a v.g. tethered to a 2nd protein • bond occasionally break --> enters cell nucleus Working together • Way genes are packaged influences transcription • Nucleosomes: DNA wrap around histones (large globular proteins) • Other proteins: Stabilise the DNA & build up chromosome • interactions w/ proteins --> some genes more accessible • e. mech but same biological response e. to thyroid • Test tube & culture studies: thyroid receptors --> off certain growth-related genes • Part-time trans fac • NF-k B • usu.----------------• Fruit flies embryos: “Dorsal” (trans fac) • Different levels --> either development of muscles / internal organs / skin / nervous tissues • ∴Different levels switch on diff. Have trans facs become increasingly important w/ the evo of complex organisms? • “if %of trans fac in higher org more than lower org = same computer. job = role in inflammation and immunity • cell fluid. diff.some leukaemia and syndromes that affect nervous system development linked to defects in homeodomain trans facs • --> mice studies • เพ้อ (Eng: waffly) . along the way) e. [Wiki.Imprinted alleles are silenced.interfering w/ a single trans fac --> no bio response] -----------5th p. sets of genes Mech: interact w/ 2 other trans fac • • --> 3 different binding sites on DNA • (on/off α spacing btw sites & presence of other trans facs) • Behaving receptors for hormones (binding --> change role) • e.-------------------Q. large class of trans fac (homeodomain trans fac) • Regulate clusters along the chromosome in a sequence that corresponds to the order .of the body parts whose development they ctrl • Genetic diseases. from Medical app: Which one have greatest impact? • • Cracked gene expression in 10-15 years --> better picks • (answers intellectual qs. methylation = shield against transcription -> “genomic imprinting” • **Genomic imprinting: The phenomenon of parent-of-origin gene expression.