BIOL 2131 Lecture Notes - Lecture 18: Chromatin, Sv40, Euchromatin

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

Document Summary

!you!then!use!only!one!of!those!strands!as!the! template!strand!for!rna. ! transcribed!genes: hence,!protein!wrapped!up!in!nucleosomes!presents!problems, genes!that!are!transcribed!contain!nucleosomes!at!same!frequency!as!nonk, all!evidence!so!far!has!shown!that!whether!or!not!the!gene!is!transcribed,!the, very!similar!to!dna!replication!and!dna!polymerase,!when!rna!polymerase!gets! access!to!the!template:!histones!are!removed!and!then!put!back!on!right!after!the! complex!moves!through!that!region! number!of!nucleosomes!is!the!same! nucleosome, however,!histones!are!displaced!by!rna!polymerase!and!reform!immediately!after!it, similar!to!replication,!other!proteins!aid!in!histone!assembly!and!removal, protein!called!fact! (facilitates!chromatin!transcription)!leads!to!h2akh2b!loss!from, fact!may!also!aid!in!dimmer!formation!after!rna!polymerase!passes, there!are!some!rare!cases!of!very!very!heavily!transcribed!genes!that!don"t!have, some!heavily!transcribed!genes!are!devoid!of!nucleosomes, for!the!vast!majority!of!genes,!there"s!the!same!frequency!of!nucleosomes!whether! nucleosomes! passes! transcribed!or!not! the!enzyme, see!figure!10. 44!!!shows!a!nucleosome!(300!kd)!and!an!rna!polymerase! (500!kd), they!form!a!massive!complex!and!then!the!dna!is!actually!fed!through!the!mouth!of, see!figure!10. 45!! !if!there!are!no!nucleosomes,!its!called!a!dnase! hypersensitive!site! (e. g. !dnasei): dnase!hypersensitive!site:!regions!on!dna!that!are!100x!more!sensitive!to!nucleases, why, dna!has!to!be!accessible!to!transcription!machinery, most!active!genes!have!hypersensitive!sites!within!promoters!during!transcription, hypersensitive!sites!may!be!free!form!histones!but!may!contain!other!proteins, they!can!have!proteins!associated,!but!they"re!generally!not!as!tightly!bound!as, dnase!sensitivity!indicates!a!change!in!chromatin!structure! nucleosomes!are, e. g. !simian!virus! (sv40)!has!nucleosome!free!region!in!promoter!of!viral!dna! !the!sv40!chromosome!ahs!a!nucleosome!gap: circular!genome!of!about!5000!bases, there"s!only!one!region!that!isn"t!very!wrapped!up:!promoter,! which!drives!the!reaction!of!genes!to!the!left!and!to!the!right. , studies!on!sv40!really!led!to!huge!discoveries!about!how!our! promoters!work!(it"s!a!viral!promoter!but!it!lives!in!mammalian!cells). , studies!show!that!enhancer!sequences!are!quite!common!in!mammals. Enhancers!were!first!discovered!in!sv40! and!chromatin!structure!are!insulators: elements!that!act!to!define!specific!chromatin!states, dna!sequences!that!restrict!the!effects!of!regulatory!elements!on!gene!expression, they"re!dna!sequencers!that!restrict!chromatin!structure!and!access!to!different! regulatory!elements!that!control!gene!structure!(i. e. !promoters,!enhancers,!etc), there!are!2!types:, 1. !insulators!located!between!enhancer!and!promoter!!!block!transcription! Thus,!at!some!point,!there!must!be!a!boundary!element!that!stops! euchromatin!from!being!influenced!by!heterochromatin!and!vice! versa. !hence,!this!is!the!use!of!insulators,!i. e. !things!that!block!or!act! as!a!boundary. : see!figure!10. 51, see!figure!10. 52!!!euchromatin!region!is!looser! (only!3)!compared!to! heterochromatin,!which!is!tighter!(has!5). Drosophila)insulators:: there!are!2!insulators!that!flank!2!important!genes!for!hsp70, 18!kb!chromosome!region!that!contains!2!insulators!that!flank!2!genes! (for!hsp70), the!insulators!are!called!scs! (specialized!chromatin!structures), contain!regions!that!are!highly!resistant!and!highly!sensitive!to!dnaase!i, scs!elements!insulate!gene!from!neighboring!dna!regions, they!act!as!barriers!to!protect!the!expression!of!the!genes!found!in!the!area!that, restrict!chromatin!effects!from!passing!into!hsp70!region, don"t!seem!to!be!positive!or!negative,!but!simply!protect!gene!region!from, see!figure!10. 53!!!what!does!sensitivity!say!about!them? surrounding!effects! they!cover! zw5!for!scs), scs!regions!contain!specific!sequences!that!bind!proteins!(e. g. !beafk32!for!scs"!an, the!ultimate!experiment,!which!they!did:!take!the!whole!region!and!move!it! somewhere!else!in!the!genome! Just!because!you!get!one!copy!from!each!parent,!it!doesn"t!mean!that!both!will!be! expressed!or!at!all: this!is!a!problem:!depending!which!one!you!get!from!your!parents,!this!could, modifications!on!histones:!absolutely!critical, genetic!inheritance!that!has!different!states! (may!have!different!phenotypes),, due!to:!o dna!methylation! without!any!change!in!dna!sequence, heterochromatin!propagation, microrna!expression! !the!example!in!the!book!pertains!to!fur!color: dosage!compensation:!chapters!29! (pages!837k838), genomic!imprinting:!chapters!29! (pages!846k848), modification!of!chromatin!on!the!histones, see!figure!29. 11!!!one!x!chromosome!is!inactivated!at!random, you!have!2!x!chromosomes!that!are!active!and!contain!different!colors. !if!you! imprint!something,!the!expression!of!that!gene!is!essentially!blocked!or!tagged!in!a! way!that!you!know!if!it!will!be!on!or!off!depending!if!you!get!that!gene!from!your! mother!or!father: there!are!now!several!examples!where!this!is!the!case, paternal!and!maternal!alleles!are!differentially!methylated!at!fertilization, whether!or!not!there!are!maternal!or!paternal!alleles!that!are!methylated!at! fertilization. !this!makes!sense,!because!in! that!way!the!regulatory!mechanisms!that!control!imprinting!can!be!better! expressed: 17!imprinted!genes!known!in!mouse! !underestimate! (now!over!70!genes!in!human! and!growing), see!figure!29. 23!! !it"s!a!very!important!evolutionary!mechanism! that!organisms!use!to!regulate!the!maternal/paternal!expression!of!different! genes. ! to!inactivate!the!gene: there!is!paternal!sperm,!maternal!egg!and!the!embryo, the!embryo!is!shown!at!the!top, one!gene!is!exemplified, maternal!is!grey!and!paternal!is!green, me!is!the!methyl!group,!which!is!put!on!the!maternal!allele, the!paternal!allele!is!still!activated, hence,!the!embryo!receives!an!active!paternal!allele, this!is!not!sexklinked! Insulin-like growth factor (igf-ii)- causes growth of cells. In!summary,!paternal!gene!is!supplying!the!hormone!and!the!maternal!gene! supplying!the!receptor. : why?!!evolutionary!reason?!size!of!fetus, some!brain!imprinted!genes!change!expression!after!birth, may!explain!some!behaviour!and!mental!disorders! (autism!and! schizophrenia)! !can!that!actually! impart!a!disease!sensitivity!to!you,!2!generations!later?!the!answer!is!yes. : how?!how!is!that!possible?, effect!of!difficult!environmental!conditions!in!early!years!(e. g. !starvation)!to, paternal!grandsons!of!men!exposed!to!famine!as!youth!had!lower!rates!of! negative!health!effects!on!descendants! cardiovascular!disease!but!higher!rates!of!diabetes!if!food!was!plentiful!