BIOL 2131 Lecture Notes - Cortisol, Nucleosome, Repressor

• School: University of Windsor
• Department: Biological Sciences
• Course: BIOL 2131
• Professor: Hubberstey

Document Summary

Important)concepts)for)week)#12:: what!controls!when!a!gene!is!turned!on, what!types!of!transcription!factors!exist!in!a!cell! at!varies!times!in!the!cell!during!development, transcription!factors, transcription!factors!are!the!proteins!that!assist!in!turning!on!various!genes, basal!factors! (tf2d,!taff200)!recruit!rna!polymerase!to!know!where!a! promoter!is. !the! mitochondria!should!be!of!one!type!and!the!genome!should!be!another!type! (if!mom!was!neanderthal!and!dad!was!human). : article:!http://news. discovery. com/human/evolution/n!eanderthalpskeletonp providespevidencepofp!interbreedingpwithphumansp130327. htm! properties, they!found!bones!that!exhibit!completely!neanderthal!and!human, female!child!with!neanderthal!mitochondria, clearly,!it!appears!that!she!was!the!love!child!of!human!and!neanderthal, there!are!about!200!nucleotide!differences!between!neanderthals!and, this!bone!was!found!in!northern!italy,!where!neanderthals!used!to!live! If!a!gene!is!transcribed,!u!could!still!regulate!the!amount!of!regulation!via!several! mechanisms!outlined!below: gene!activation!can!be!controlled!at!many!levels:, chromatin!structure!changes, transcriptional!activation, control!of!splicing!and!rna!transport, rna!stability, translational!control! !control!of!transcription!initiation:!used!for!most!genes! some!transcription!factors!are!in!our!cells!all!the!time,!but!they!don"t!turn!on! those!genes!all!the!time! !i. e. !something!must!be!regulating: there!are!many!different!layers!of!gene!expression!control, you!can!have!chromatin!regulation, regulate!transcription!factor!access!to!the!dna! transcription! Tatabox! (see!last!lecture): 1. !basal!factors:!rna!polymerase!and!associated!factors!that!bind!to!startpoint!and, 2. !activators:!proteins!that!recognize!short!specific!sequences!that!can!activate, usually!found!in!enhancers,!but!generally!upstream!of!the!startpoint!and, these!are!really!the!players!that!activate!transcription!by!communicating! their!presence!to!the!basal!factors, can!be!always!in!cell! (ubiquitous), only!present!at!special!times!and!in!specific!cells, main!difference!between!activators!is!that!coactivators!do!not!bind!dna, 3. !coactivators:!do!not!bind!dna!but!connect!activators!with!basal!factors! Tatabox!regions: 4. !chromatin!regulators:!alters!nucleosome!state!to!allow!transcription, can!actually!affect!the!chromatin!state!in!that!particular!region!where!the, they!affect!histone!structure!or!state:!acetylation,!methylation,!etc! gene!is! themselves! elements, recognize!specific!sequences!in!enhancers,!promoters!and!other!regulatory, after!binding!dna,!activators!interact!with!other!factors!(e. g. !tafs!and!tfiib), most!activators!have!3!functional!domains:, dna!binding!domain! (they!all!have"to"bind!dna), connecting!domain, transcription!activation!domain! structure, can!think!of!them!as!3!blobs!of!protein!all!encoded!by!one!gene!but!have!a!tripartite, domains!act!independently! (can!be!swapped!between!other!activators!using, see!figure!28. 7! recombinant!dna!technology), some!activators!do!not!contain!activation!domains, have!to!interact!with!specific!coactivators!to!initiate!transcription, a!rare!event,!but!has!been!shown!to!occur!in!some!instances, red!=!one!protein, see!figure!28. 8!! How)can)transcriptional)activators)become)active?: 1. !only!become!expressed!when!needed, 2. !activated!by!phosphorylation!(e. g. !hstf), 3. !activated!by!binding!a!ligand!(e. g. !steroid!hormone), 3. !activated!by!binding!a!ligand!(e. g. !steroid!hormone)! i. e. !cortisol,!cortisone, 4. !activity!blocked!by!inhibitor!which!binds!activator, 5. !activity!works!as!a!dimer!with!specific!partners, 6. !precursor!inactive!molecule!is!cleaved!into!active!factor, see!figure!28. 2!(describes!1. !to!6. !in!order): types!are!based!on!different!dna!binding!domains, different!protein!structures, 1. !zincpfinger, 2. !steroid!receptors, 3. !helixpturnphelix, 4. !helixploopphelix, 5. !leucine!zippers! and!binds!a!zn!binding!site, formed!by!a!23!amino!acid!region!that!contains!cys!and!his!amino!acids! (cys2/hys2), see!figure!28. 11! (left), see!figure!28. 10!(right)!! Homeodomain)transcription)activators:) that!activate!gene!transcription: small!hormones!that!activate!many!cellular!processes!through!binding!receptors, each!specific!receptor!can!activate!different!genes, each!receptor!binds!specific!ligand!and!then!enters!nucleus!and!binds!to!promoter, receptors!have!conserved!structure, npterminal!activation!domain, middle!dna!binding!domain, cpterminal!hormone!binding!domain! sequences! sequences!in!promoters!of!genes!involved!in!the!development, contains!highly!conserved!60!amino!acid!region! (homeobox)!that!binds!to!specific, member!of!the!helixpturnphelix!family!of!activators, most!are!activators!but!some!have!repressor!domains!attached!to!dna!binding, homeobox!factors!control!developmental!pathways!in!eukaryotes, what!do!homeobox!activators!do!if!mutated, drosophila!was!first!example!of!homeobox!genes! (1983), see!picture!!!mrna!of!fzt. !the!homeodomain!has!three!alpha!helices: see!figure!(right)!!!the!homeodomain!is!a!module!of!60!amino!acids! containing!proteins), all!leucine!zipper!containing!activators!dimerize! (they!bind!other!leucine!zippers, stretch!of!leucines!that!provide!dimerization!motif! (bzip!domain), leucines!are!present!every!7!amino!acids! (leupx6), bzip!domain!also!contains!basic!region!which!interacts!with!dna, hence,!leucine!zipper!itself!doesn"t!bind!to!dna, can!form!homodimers!(with!themselves)!or!heterodimers! (interacting!with!another! leucine!zipper!activator)! !depending!on!which!one,!it"ll!change!the!sequence!of!dna! that!they!can!bind!to, c/ebp!binds!to!caat!box, jun!and!fos!bind!to!ap1!sites!in!promoters!