I-Epigenetics ku-Gene Regulation
I-Epigenetics igatsha lebhayoloji elifunda izinguquko emsebenzini wezakhi zofuzo ezingabangelwa izinguquko ekulandeleni kwe-DNA. Ngamanye amazwi, i-epigenetics ichaza ukuthi izakhi zofuzo zingavulwa noma zivalwe kanjani ngaphandle kokushintsha ikhodi yezakhi zofuzo ngokwayo. Lo mqondo ubalulekile ngoba usisiza siqonde ukuthi kungani amangqamuzana emzimbeni abelana nge-DNA efanayo angaba nemisebenzi ehlukene, njengamaseli ezinzwa, amangqamuzana emisipha, namaseli egazi. I-Epigenetics idlala indima enkulu ekulawulweni kwezakhi zofuzo, inqubo yokulawula ukuthi izakhi zofuzo zibonakaliswa nini, kuphi, nokuthi zinamandla kangakanani.
Izisekelo Zokulawulwa Kwezakhi Zofuzo
Ukulawulwa kwezakhi zofuzo kuyindlela esetshenziswa amaseli ukulungisa ukukhiqizwa kwamaprotheni ngokwezidingo. Izakhi zofuzo "ezisebenzayo" ziguqulwa zibe yi-RNA bese zihunyushwa zibe amaprotheni. Ngakolunye uhlangothi, izakhi zofuzo "ezingasebenzi" azikhiqizi imikhiqizo esebenzayo. Lo mthetho ubalulekile ekuthuthukisweni kombungu, ukuhlukaniswa kwamaseli, impendulo yokucindezeleka, ukuzivumelanisa nemvelo, kanye nokugcinwa kwemisebenzi yomzimba. Ukuphazamiseka kokulawulwa kwezakhi zofuzo kungaholela ezifweni ezahlukahlukene, okuhlanganisa umdlavuza, ukuphazamiseka kwe-metabolic, kanye nokukhubazeka kokukhula.
Kulesi simo, i-epigenetics isebenza njengohlelo olwengeziwe lokulawula phezu kwe-genome. Uma i-genome ifana nencwadi yeresiphi, khona-ke i-epigenetics iwuphawu noma inothi elinquma ukuthi yiziphi izindlela zokupheka okufanele uzifunde nokuthi kangaki.
Izindlela Eziyinhloko Ze-Epigenetics
Izindlela eziningana ezinkulu ze-epigenetic zithonya ukulawulwa kwezakhi zofuzo. Ezintathu ezifundwe kakhulu yi-DNA methylation, ukuguqulwa kwe-histone, kanye nokulawulwa yi-non-codeing RNA. Zonke ezintathu zisebenza ngendlela ehlelekile ukulawula ukufinyeleleka kwe-DNA kanye namazinga okuvezwa kwezakhi zofuzo.
1. I-DNA methylation
I-methylation ye-DNA yenzeka lapho iqembu le-methyl (—CH₃) lingezwa esisekelweni se-cytosine, ngokuvamile ezindaweni ze-DNA ezicebile ngama-base pairs e-CpG (cytosine-phosphate-guanine). Ukwengezwa kwaleli qembu le-methyl kuvame ukuhlotshaniswa nokucindezela ukubonakaliswa kwezakhi zofuzo. Izindawo ezibaluleke kakhulu ze-methylation ngokuvamile yizikhuthazi zezakhi zofuzo, izifunda ze-DNA ezilawula ukuqaliswa kokubhalwa.
Uma i-promoter ine-methylation eningi, izici zokubhala ziba nobunzima bokubopha, futhi i-RNA polymerase ayikwazi ukusebenza kahle. Ngenxa yalokho, i-gene ivame "ukuthula." I-DNA methylation idlala indima ebalulekile ezinqubweni ezijwayelekile ezifana nokungasebenzi kwe-X chromosome kwabesifazane kanye nokushicilelwa kwe-genomic, lapho ukuvezwa kwezakhi zofuzo kuthonywa khona ukuzalwa kwabazali.
2. Ukuguqulwa kwe-Histone
I-DNA ekwi-nucleus yeseli ayimane ibole; kunalokho, ihlanganiswa kanye namaprotheni e-histone ukuze kwakhiwe i-chromatin. Lesi sakhiwo singaba siqinile noma sikhululeke. Uma i-chromatin iqinile (i-heterochromatin), izakhi zofuzo azifinyeleleki kalula futhi azibonakali kalula. Uma i-chromatin ikhululekile (i-euchromatin), izakhi zofuzo zifinyeleleka kalula futhi ziyasebenza kakhulu.
Ama-Histone angaguqulwa ngamakhemikhali ahlukahlukene, njenge-acetylation, i-methylation, i-phosphorylation, kanye ne-ubiquitination. I-histone acetylation, ikakhulukazi kuma-lysine residues, ivame ukuhlotshaniswa nokusebenza kwezakhi zofuzo ngoba ibangela ukuthi i-chromatin ivuleke kakhulu. Ngokuphambene nalokho, i-histone methylation ingabangela ukusebenza noma ukucindezelwa kuye ngendawo kanye nenani lamaqembu e-methyl angeziwe. Ukuhlanganiswa kwalezi zinguquko kwakha "ikhodi ye-histone" esiza ekunqumeni isimo sokubonakaliswa kwezakhi zofuzo.
3. I-RNA engabhalisi
Akuwona wonke ama-RNA ahunyushwa abe yiprotheni. Ama-RNA amaningi angabhalisi adlala indima ekulawulweni kwezakhi zofuzo, okuhlanganisa ama-microRNA (ama-miRNA), ama-RNA amade angabhalisi (ama-lncRNA), kanye nama-RNA amancane aphazamisayo (ama-siRNA). Ama-MicroRNA, isibonelo, anganamathela kuma-mRNA aqondiwe futhi abangele ukuwohloka noma ukuvimbela ukuhumusha, ngaleyo ndlela anciphise ukukhiqizwa kwamaprotheni.
Ama-RNA angabhalisi futhi angaqondisa ama-protein complex e-epigenetic ezindaweni ezithile ku-genome, ngaleyo ndlela ethonya i-DNA methylation noma ukuguqulwa kwe-histone. Ngale ndlela, ama-RNA angabhalisi asebenza njengabalawuli abalungisiwe abanquma amazinga athile okubonakaliswa kwezakhi zofuzo.
I-Epigenetics Ekuthuthukisweni Kwamaseli Nokwehluka
Enye yezindima ezivelele kakhulu ze-epigenetics isekuthuthukisweni kwezinto eziphilayo. Njengoba i-zygote ikhula ibe izinhlobo ezahlukene zamaseli, iseli ngalinye liphethe i-DNA efanayo kodwa linohlelo oluhlukile lokubonakaliswa kwezakhi zofuzo. Lolu hlelo lusungulwa futhi lugcinwe ngamamaki e-epigenetic.
Isibonelo, amaseli e-stem ane-chromatin evulekile, evumela izakhi zofuzo eziningi ukuthi zisebenze. Njengoba zihluka, amamaki e-epigenetic anciphisa ukukhetha kwezakhi zofuzo ezisebenzayo, okuvumela amaseli ukuthi abe ngochwepheshe, njengezakhi zofuzo zesibindi ezivuselela ubuthi noma amaseli e-pancreatic avuselela izakhi zofuzo ezikhiqiza i-insulin.
Ithonya Lemvelo ku-Epigenetics
I-Epigenetics iphinde ivale igebe phakathi kwezakhi zofuzo kanye nendawo ezungezile. Izici ezifana nokudla okunempilo, ukucindezeleka, ukuchayeka ebuthi, ukubhema, umsebenzi womzimba, ngisho namaphethini okulala kungathinta izimpawu ze-epigenetic. Isibonelo, ukuntuleka kwezakhi ezithile ezisebenza njengabanikeli be-methyl (njenge-folate ne-vitamin B12) kungathinta amaphethini e-methylation ye-DNA.
Ukuchayeka ezintweni ezingcolisayo noma kumakhemikhali nakho kungashintsha ukuguqulwa kwe-histone kanye ne-DNA methylation, ekugcineni kube nomthelela engcupheni yesifo. Lesi esinye sezizathu ezenza indlela yokuphila ibe nomthelela empilweni yesikhathi eside, ngisho nasezingeni lama-molecule.
I-Epigenetics kanye Nezifo
Ukungalingani ekulawulweni kwe-epigenetic kungaba nomthelela ezifweni ezahlukahlukene. Emdlavuzeni, amaphethini e-methylation ye-DNA avame ukubhekana nezinguquko ezinkulu. Amanye ama-gene okucindezela isimila angathuliswa ngenxa ye-promoter hypermethylation, okuphuca amaseli izindlela zokulawula ukukhula. Ngakolunye uhlangothi, ezinye izindawo ze-genome zingaba yi-hypomethylated, okuholela ekungazinzini kwe-chromosome.
Ngaphezu komdlavuza, ukuphazamiseka kwe-epigenetic kuhlotshaniswa nezifo eziwohloka kwemizwa njenge-Alzheimer's kanye ne-Parkinson's, izinkinga ze-metabolic ezifana nesifo sikashukela sohlobo 2, kanye nezifo zokuzivikela komzimba. Ngisho nezinye izifo zokukhula ezifana ne-Prader-Willi kanye ne-Angelman syndromes zihlotshaniswa ne-epigenetic genomic imprinting.
I-Epigenetics njengenhloso yokwelapha
Ngenxa yokuthi izinguquko ze-epigenetic ziyaguquguquka, ziyinhloso ekhangayo yokuthuthukiswa kwemithi. Izindlela zokwelapha eziningana zomdlavuza sezivele zisebenzisa izithibi zama-enzyme ahilelekile ku-DNA methylation noma i-histone deacetylation, njengezithibi ze-DNMT kanye nezithibi ze-HDAC. Le mithi ingavuselela ukubonakaliswa kwezakhi zofuzo ezithulile, kufaka phakathi izakhi zofuzo ezicindezela isimila.
Kodwa-ke, ukwelashwa kwe-epigenetic kuletha izinselele ngoba izinguquko ze-epigenetic zingenzeka ezizakhini eziningi zofuzo ngesikhathi esisodwa. Kudingeka amasu anembile kakhulu ukuze kufezwe imiphumela eqondiwe futhi kuncishiswe imiphumela emibi. Ukuthuthukiswa kobuchwepheshe obufana nokuhlela i-epigenome okusekelwe ku-CRISPR nakho sekuqala ukuvula amathuba okushintsha amamaki e-epigenetic ezindaweni ezithile zofuzo ngaphandle kokusika i-DNA.
I-Epigenetics Efa
Umbuzo owodwa othakazelisayo ukuthi izinguquko ze-epigenetic zingazuzwa yini njengefa. Kwezinye izinto eziphilayo, izimpawu ezithile ze-epigenetic zingaqhubeka ezizukulwaneni ngezizukulwane. Kubantu, izimpawu eziningi ze-epigenetic "zibuyiselwa" ngesikhathi sokwakheka kwe-gamete kanye nokukhula kombungu kwasekuqaleni. Kodwa-ke, kunezinkomba zokuthi ezinye izinguquko ezithile zingazuzwa njengefa ngezindlela eziyinkimbinkimbi, yize lokhu kusalokhu kuyindawo esebenzayo yocwaningo.
Isiphetho
I-Epigenetics iyisici esibalulekile ekulawulweni kwezakhi zofuzo ngoba inquma amazinga okufinyelela kwe-DNA kanye nokubonakaliswa kwezakhi zofuzo ngaphandle kokushintsha ukulandelana kwezakhi zofuzo. Ngokusebenzisa i-methylation ye-DNA, ukuguqulwa kwe-histone, kanye ne-RNA engabhalisi ikhodi, amaseli angalawula ngokuguquguqukayo ukusebenza kwezakhi zofuzo ngokwezidingo zokuthuthukiswa kanye nezimpendulo zemvelo. Ukuqonda i-epigenetics kusiza ukuchaza ukuhlukaniswa kwamaseli, ithonya lendlela yokuphila empilweni, kanye nemvelaphi yezifo ezahlukahlukene. Ngaphezu kwalokho, i-epigenetics inikeza amathuba abalulekile kwezokwelapha, ikakhulukazi ngenxa yemvelo yayo eguquguqukayo. Ngocwaningo oluqhubekayo, i-epigenetics inamandla okuba yisisekelo esibalulekile sokwelashwa okunembile kakhulu kanye nokwenzelwe umuntu siqu esikhathini esizayo.
