Ama-Histones kanye nesakhiwo se-Chromatin
Ku-nucleus yeseli le-eukaryotic, i-DNA ayikho "njengomucu" oshiywe wodwa. Ukube yonke i-DNA yomuntu ibingasongwa, ibizoba ngamamitha amabili ubude, yize i-nucleus ingamamitha ambalwa kuphela ububanzi. Ukuze ivumelane naleli nani elikhulu lezinto zofuzo ngenkathi ihlala ifinyeleleka ezinqubweni ezibalulekile zebhayoloji, amaseli anesistimu yokupakisha ehlelekile neguquguqukayo. Lolu hlelo lwaziwa ngokuthi i-chromatin, futhi izingxenye zalo ezibalulekile yi-histones—amaprotheni amancane, ashaje kahle asebenza njengezimbobo lapho i-DNA iboshwe khona. Ukuqonda i-histones kanye nesakhiwo se-chromatin kusisiza sichaze ukuthi izakhi zofuzo zivulwa noma zivaliwe kanjani, ukuthi amaseli ahlukana kanjani, nokuthi kungani izinguquko ezincane ekupakishweni kwe-DNA zingaxhunyaniswa nezifo.
Kuyini i-chromatin?
I-Chromatin iyinhlanganisela eyakhiwe yi-DNA, amaprotheni (ngokuyinhloko ama-histone), kanye nenani lamaprotheni angewona ama-histone kanye ne-RNA ehlobene nayo. Umsebenzi oyinhloko we-Chromatin awugcini nje ngokupakisha i-DNA kodwa futhi nokulawula ukufinyelela kolwazi lwezakhi zofuzo. I-Chromatin ingapakishwa kakhulu noma ipakishwe kalula, futhi lesi simo sithonya ukuthi izakhi zofuzo ezithile zifundwa kalula (zibhalwe phansi) noma zivame ukuhlala zithule.
Ngokuvamile, kunezinhlobo ezimbili ze-chromatin ezivame ukuxoxwa ngazo:
1. I-Euchromatin: isakhiwo esikhululekile, esicebile ngezakhi zofuzo, futhi esisebenza kakhulu ekubhalweni.
2. I-Heterochromatin: isakhiwo esiminyene, esivame ukuqukethe ukulandelana okuphindaphindiwe, futhi ngokuvamile esingasebenzi kangako ekubhalweni. I-Heterochromatin idlala indima ebalulekile ekugcineni ukuzinza kwe-genome, isibonelo ezifundeni ze-centromere kanye ne-telomere.
Kubalulekile ukugcizelela ukuthi i-euchromatin ne-heterochromatin akuzona izigaba eziqinile; i-chromatin ingashintsha ngokuya ngezidingo zamaseli, isigaba somjikelezo weseli, kanye nezimpawu zemvelo.
Ama-Histones: amaprotheni ayinhloko ahlanganisa i-DNA
Ama-Histones amaprotheni acebile ngama-amino acid ashajwe kahle njenge-lysine ne-arginine. Lokhu kushajwa okuhle kubalulekile ngoba i-DNA ishajwe kabi ngenxa yamaqembu e-phosphate emhlane wayo. Ukusebenzisana kwe-electrostatic phakathi kwama-histones ne-DNA kusiza ekwakheni isakhiwo esizinzile sokupakisha.
Ama-histone ayinhloko ahlukaniswe ngamaqembu amabili:
– Ama-core histones: H2A, H2B, H3, kanye ne-H4. Lawa amane akha “i-core” lapho i-DNA igoqeke khona.
– Ama-Linker histones: ikakhulukazi i-H1 (kanye nezinhlobo zayo). Lawa ma-histones asiza ekuqiniseni ukuxhumana kwe-DNA phakathi kwama-nucleosomes futhi akhuthaze amazinga aphezulu okupakishwa.
Ngaphezu kwama-histone "acanonical", kukhona nezinhlobo ze-histone (isb., i-H2A.Z, i-H3.3, i-CENP-A) ezingathatha indawo yama-histone avamile ezindaweni ezithile. Lezi zinhlobo zinikeza izakhiwo ezithile ku-chromatin, njengokusekela ukusebenza kwezakhi zofuzo, impendulo yomonakalo we-DNA, noma ubunikazi be-centromere.
I-Nucleosome: iyunithi eyisisekelo yesakhiwo se-chromatin
Iyunithi yesakhiwo eyisisekelo kakhulu ye-chromatin yi-nucleosome. I-nucleosome yakhiwa yilokhu:
- I-Histone octa-mer: 2 × (H2A, H2B, H3, H4)
– I-DNA izungezwe i-octa-mer engaba ngu-147 base pairs (bp)
– I-DNA ethi “Linker” enobude obuhlukahlukene (ngokuvamile engaba ngu-20–80 bp), exhumanisa i-nucleosome eyodwa nenye
Ukuze usebenzise isifaniso, i-DNA ifana nentambo, kuyilapho ama-nucleosome efana nama-beads. Lesi sakhiwo sivame ukubizwa ngokuthi “ama-beads-on-a-string” futhi simelela izinga lokuqala lokupakisha.
Indima yama-nucleosome ayiyona nje i-mechanical. Ngenxa yokuthi i-DNA ezungezwe ama-histone ayitholakali kalula, ukuba khona kanye nendawo yama-nucleosome kunganquma ukuthi izici zokubhala kanye namanye ama-enzyme zingabopha yini i-DNA. Ngamanye amazwi, ama-nucleosome “amasango” angavula noma avale ukufinyelela kuma-gene.
Amazinga okupakishwa kwe-Chromatin
Ngemva kwezinga le-nucleosome, i-chromatin ingahlanganiswa kakhulu. Ngokwesiko, izincwadi zichaza ukupakisha okunezinga elihlukahlukene:
1. I-DNA double helix (2 nm)
2. Imicu ye-Nucleosome (cishe i-10–11 nm)
3. I-fiber engu-30 nm (imodeli ye-solenoid noma ye-zig-zag; ukuba khona kwayo ezimweni zamaseli aphilayo kusaxoxwa ngakho, kodwa umqondo wokuqina okuthuthukisiwe usabalulekile)
4. Isizinda se-Loop: imicu ye-chromatin yakha ama-loop anamathele ohlakeni lweprotheni ku-nucleus.
5. Ama-chromosome e-Metaphase: uhlobo oluqinile kakhulu ngesikhathi sokuhlukaniswa kwamaseli.
Ngaphakathi kwe-nucleus, ukuhlelwa kwe-chromatin okunezinhlangothi ezintathu kuhlelwe kahle kakhulu. Izakhi zofuzo ezisebenzayo zivame ukutholakala ezindaweni ezinobungani bokuqoshwa kwezakhi zofuzo, kuyilapho izindawo ezithule zingahlanganiswa ezindaweni ezithile. Le nhlangano isiza ekuhleleni ukuvezwa kwezakhi zofuzo ngendlela ephumelelayo.
Ukuguqulwa kwe-Histone kanye "nekhodi ye-histone"
Ingxenye evame ukuguqulwa kakhulu ye-histone umsila we-histone, okuyi-N-terminal segment ephuma ku-nucleosome. Lo msila ungadlula ezinguqulweni ezahlukahlukene ngemuva kokuhumusha, isibonelo:
– I-Acetylation: ngokuvamile ku-lysine; ivame ukunciphisa ukushaja okuhle kwama-histone ukuze isibopho ne-DNA sibe buthaka futhi i-chromatin ivuleke kakhulu, evame ukuhlotshaniswa nokusebenza kwezakhi zofuzo.
– I-Methylation: ku-lysine noma ku-arginine; umphumela uncike endaweni. Isibonelo, i-methylation ku-H3K4 ivame ukuhlotshaniswa nezakhi zofuzo ezisebenzayo, kuyilapho i-H3K9 noma i-H3K27 ivame ukuhlotshaniswa nokuthulisa.
– I-Phosphorylation: ivame ukuhlotshaniswa nokusabela komonakalo we-DNA kanye nokulawulwa kwe-mitosis.
- Ubiquitination kanye nezinye izinguquko ezithinta ukuzinza kwe-chromatin kanye nokusebenzisana.
Leli qoqo lamaphethini okuguqulwa livame ukubizwa ngokuthi “ikhodi ye-histone,” umqondo uwukuthi inhlanganisela ethile yokuguqulwa “ingafundwa” ngamanye amaprotheni ukuze kukhiqizwe imiphumela ethile yezinto eziphilayo—isibonelo, ukuqasha ama-complexes e-transcriptional activator, ama-complexes e-repressor, noma amaprotheni okulungisa i-DNA.
Ukuguqulwa kwe-Histone kulawulwa amaqembu amathathu amaprotheni:
– Abalobi: ama-enzyme aneza izinguquko (isib. i-HAT ye-acetylation, i-HMT ye-methylation)
– Izisuli: ama-enzyme asusa izinguquko (isib. i-HDAC yokususa i-acetylation, i-demethylase)
– Abafundi: amaprotheni aqaphela ukuguqulwa (isb. ama-bromodomain aqaphela i-acetylation)
Ukulungiswa kwe-Chromatin: ukushintsha ama-nucleosome ukuze kulawulwe izakhi zofuzo
Ngaphezu kokuguqulwa kwamakhemikhali, amaseli abuye abe nama-complexes okulungisa kabusha i-chromatin asebenzisa amandla e-ATP ukushintsha isikhundla noma ukwakheka kwama-nucleosome. La ma-complexes angenza okulandelayo:
– Ukushintsha ama-nucleosome (ukushelela) ukuze izindawo ezithile ze-DNA zivuleke/zivalwe
- Ukususa noma ukufaka esikhundleni ama-histone ngezinhlobo ezahlukene
- Ilawula ibanga phakathi kwama-nucleosome
Ukulungiswa kabusha kubalulekile lapho izakhi zofuzo zidinga ukuvuselelwa ngokushesha, lapho i-DNA idinga ukuphindwa, noma lapho kwenzeka umonakalo we-DNA odinga ukufinyelela kuma-enzyme okulungisa.
Ama-Histones, ukuphindaphindwa kwe-DNA, kanye nokulungiswa komonakalo
Uma amangqamuzana ephinda i-DNA, i-chromatin kumele ihlukaniswe okwesikhashana phambi kwefoloko lokuphindaphinda bese ihlanganiswa kabusha ngemuva kwayo. Ama-histone amadala namasha asatshalaliswa ku-DNA yendodakazi, esizwa amaprotheni e-histone “chaperone”. Le nqubo ayibandakanyi nje kuphela ukupakisha kabusha kodwa futhi ihilela “inkumbulo” yokulawulwa kwezakhi zofuzo (isb., amaphethini okuguqulwa kwe-histone) ukuze kugcinwe ubunikazi beseli obuzinzile.
Ekulungiseni umonakalo we-DNA, i-chromatin nayo iyashintshashintsha. Umonakalo onjengokuphuka kwezintambo ezimbili udala izimpawu eziguqula ama-histone athile (isb., i-phosphorylation ye-H2A.X kuma-eukaryotes amaningi) ukuze kuqashwe imishini yokulungisa. Ngaphandle kwezinguquko ze-chromatin, izindawo eziningi ze-DNA kunzima ukuzifinyelela ama-enzyme okulungisa.
I-Chromatin kanye ne-epigenetics
Ingxoxo ngama-histone ivame ukuhlangana ne-epigenetics, okuwukuguqulwa okuzuzwe njengefa kwamaphethini okubonakaliswa kwezakhi zofuzo ngaphandle kokushintsha ukulandelana kwe-DNA. Ukuguqulwa kwe-histone, ukuhlukahluka kwe-histone, kanye nezikhundla ze-nucleosome kungasebenza njengezimpawu ze-epigenetic. Kanye ne-methylation ye-DNA kanye ne-RNA engabhalisi ikhodi, lolu hlelo luvumela amaseli ane-DNA efanayo (isibonelo, amaseli emisipha namaseli ezinzwa) ukuthi abe nezinhlelo zezakhi zofuzo ezihlukile.
Ukungalawulwa kahle kwe-epigenetic kungabangela izimo ezahlukahlukene, okuhlanganisa umdlavuza, izinkinga zokukhula, kanye nezifo eziwohlokayo zemizwa. Ngenxa yokuguquguquka kwazo, izingxenye ze-epigenetic nazo ziyizinhloso zokwelapha, njengezithibi ze-HDAC noma ama-enzyme athile e-methylation, kwezinye izimo zezokwelapha.
I-Penutup
Ama-Histone kanye nesakhiwo se-chromatin kuyisisekelo esibalulekile sebhayoloji yamangqamuzana yanamuhla. Ama-Histone awawona nje “ama-wind” e-DNA, kodwa kunalokho ayizingxenye ezilawulayo ezivumela i-DNA ukuthi ihlanganiswe ngenkathi isebenza. Ngokwakheka kwe-nucleosome, ukuqiniswa okuthuthukisiwe, ukuguqulwa komsila we-histone, ukuhlukahluka kwe-histone, kanye nokuguqulwa kabusha okuqhutshwa yi-ATP, amaseli angalawula ukuthi izakhi zofuzo zivulwa nini futhi kuphi, ukuthi i-DNA iphindaphindwa kanjani, nokuthi umonakalo ulungiswa kanjani. Ngokuqonda i-chromatin dynamics, singabuka i-genome hhayi njengombhalo ongaguquki, kodwa njengombhalo ohlelwa kabusha njalo—ovulwa, ovalwe, futhi ohlelwa—ukugcina impilo yeseli ihlelekile.
