Li-Histone le Sebopeho sa Chromatin
Ka hare ho nucleus ea sele ea eukaryotic, DNA ha e eo e le "khoele" e hlephileng. Haeba DNA eohle ea motho e ne e ka phutholoha, e ne e tla ba bolelele ba limithara tse peli, leha nucleus e le bophara ba li-micrometer tse 'maloa feela. Ho lekana bongata bona bo boholo ba liphatsa tsa lefutso ha e ntse e le teng bakeng sa lits'ebetso tsa bohlokoa tsa baeloji, lisele li na le sistimi e ntle le e matla ea ho paka. Sistimi ena e tsejoa e le chromatin, 'me likarolo tsa eona tsa bohlokoa ke li-histone - liprotheine tse nyane, tse nang le charge e ntle tse sebetsang joalo ka li-spool tseo DNA e kobehileng ho tsona. Ho utloisisa li-histone le sebopeho sa chromatin ho re thusa ho hlalosa hore na liphatsa tsa lefutso li buloa kapa li tima joang, hore na lisele li arohana joang, le hore na ke hobane'ng ha liphetoho tse nyane liphuthelong tsa DNA li ka amahanngoa le lefu.
Kromatin ke eng?
Chromatin ke motsoako o entsoeng ka DNA, liprotheine (haholo-holo li-histone), le liprotheine tse 'maloa tse seng tsa histone le RNA e amanang le tsona. Mosebetsi o ka sehloohong oa Chromatin ha se feela ho paka DNA empa hape ke ho laola phihlello ea tlhahisoleseling ea liphatsa tsa lefutso. Chromatin e ka pakoa ka thata kapa ea pakoa ka mokhoa o sa tsitsang, 'me boemo bona bo susumetsa hore na liphatsa tse ling tsa lefutso li baloa habonolo (li ngotsoe) kapa li na le tšekamelo ea ho lula li khutsitse.
Ka kakaretso, ho na le mefuta e 'meli ea chromatin eo hangata e tšohloang:
1. Euchromatin: sebopeho se hlephileng, se ruile ka liphatsa tsa lefutso, 'me se sebetsa haholoanyane ka mokhoa oa ho ngola.
2. Heterochromatin: sebopeho se teteaneng, hangata se nang le tatellano e pheta-phetoang, mme ka kakaretso se sa sebetse haholo ho ngoleng. Heterochromatin e boetse e bapala karolo ea bohlokoa ho bolokeng botsitso ba genome, mohlala libakeng tsa centromere le telomere.
Ho bohlokoa ho hatisa hore euchromatin le heterochromatin ha se lihlopha tse tiileng; chromatin e ka fetoha ho latela litlhoko tsa sele, mohato oa potoloho ea sele le matšoao a tikoloho.
Histones: liprotheine tsa mantlha tse pakang DNA
Li-histone ke liprotheine tse nang le li-amino acid tse nang le positive charge tse kang lysine le arginine. Tefiso ena e ntle e bohlokoa hobane DNA e na le positive charge ka lebaka la lihlopha tsa phosphate mokokotlong oa eona. Likamano tsa motlakase pakeng tsa li-histone le DNA li thusa ho theha sebopeho se tsitsitseng sa ho paka.
Li-histone tse kholo li arotsoe ka lihlopha tse peli:
– Li-histone tsa mantlha: H2A, H2B, H3, le H4. Tsena tse 'ne li etsa "core" eo DNA e pota-potileng ka eona.
– Li-histone tsa Linker: haholo-holo H1 (le mefuta ea eona). Li-histone tsena li thusa ho tsitsisa likamano tsa DNA lipakeng tsa li-nucleosome le ho khothaletsa maemo a holimo a liphutheloana.
Ntle le li-histone tse "canonical", ho boetse ho na le mefuta e fapaneng ea li-histone (mohlala, H2A.Z, H3.3, CENP-A) e ka nkang sebaka sa li-histone tse tloaelehileng libakeng tse itseng. Mefuta ena e fana ka thepa e itseng ho chromatin, joalo ka ho tšehetsa ts'ebetso ea liphatsa tsa lefutso, karabelo ea tšenyo ea DNA, kapa boitsebiso ba centromere.
Nucleosome: yuniti ea motheo ea sebopeho sa chromatin
Yuniti ya motheo ka ho fetisisa ya sebopeho sa chromatin ke nucleosome. Nucleosome e na le:
- Histone octa-mer: 2 × (H2A, H2B, H3, H4)
– DNA e phuthetsoe ho potoloha octa-mer ea lipara tsa motheo tse ka bang 147 (bp)
– DNA ea “Linker” ea bolelele bo fapaneng (hangata e ka ba 20-80 bp), e hokahanyang nucleosome e 'ngoe le e 'ngoe
Ha re sebelisa papiso, DNA e tšoana le khoele, ha li-nucleosome li tšoana le lifaha. Sebopeho sena hangata se bitsoa "lifaha-ho-khoele" 'me se emela boemo ba pele ba sephutheloana.
Karolo ea li-nucleosome ha se ea mechine feela. Hobane DNA e phuthetsoeng ho potoloha li-histone e ba bonolo ho e fumana, boteng le boemo ba li-nucleosome li ka etsa qeto ea hore na lintho tse etsang hore li-transcription le li-enzyme tse ling li ka tlama ho DNA. Ka mantsoe a mang, li-nucleosome ke "liheke" tse ka bulang kapa tsa koala phihlello ea liphatsa tsa lefutso.
Maemo a ho paka a Chromatin
Kamora boemo ba nucleosome, chromatin e ka kopanngoa haholoanyane. Ka tloaelo, libuka tsa thuto li hlalosa ho paka ka maemo a mangata:
1. DNA double helix (2 nm)
2. Likhoele tsa nucleosome (hoo e ka bang 10–11 nm)
3. Faeba ya 30 nm (mohlala wa solenoid kapa zig-zag; boteng ba yona maemong a sele e phelang bo ntse bo buuwa, empa mohopolo wa ho teteana ho hoholo o ntse o le bohlokwa)
4. Sebaka sa sekotjana: likhoele tsa chromatin li etsa li-loop tse khomaretsoeng moralong oa protheine ka har'a nucleus.
5. Li-chromosome tsa Metaphase: sebopeho se teteaneng ka ho fetisisa nakong ea karohano ea sele.
Ka hare ho nucleus, tokisetso ea mahlakore a mararo ea chromatin e hlophisitsoe hantle haholo. Liphatsa tsa lefutso tse mafolofolo li atisa ho ba libakeng tse mosa ho ngoloa ha liphatsa tsa lefutso, ha libaka tse khutsitseng li ka "kopanngoa" libakeng tse itseng. Mokhatlo ona o thusa ho hokahanya tlhahiso ea liphatsa tsa lefutso ka katleho.
Liphetoho tsa Histone le "khoutu ea histone"
Karolo e fetoloang hangata ea histone ke mohatla oa histone, e leng karolo ea N-terminal e hlahellang ho tsoa ho nucleosome. Mohatla ona o ka fetoloa liphetoho tse fapaneng kamora phetolelo, mohlala:
– Acetylation: hangata ho lysine; e atisa ho fokotsa tjhaja e ntle ya histones e le hore tlamahano le DNA e fokole mme chromatin e bulehe haholoanyane, hangata e amanang le ho kenngwa tshebetsong ha jini.
– Methylation: ho lysine kapa arginine; phello e itshetlehile ka sebaka. Mohlala, methylation ho H3K4 hangata e amahanngoa le dijini tse sebetsang, ha H3K9 kapa H3K27 hangata e amahanngoa le ho kgutsisa.
– Phosphorylation: hangata e amahanngoa le karabelo ea tšenyo ea DNA le taolo ea mitosis.
– Ubiquitination le diphetoho tse ding tse amang botsitso le dikamano tsa chromatin.
Pokello ena ea mekhoa ea phetoho hangata e bitsoa "khoutu ea histone," khopolo ke hore metsoako e itseng ea liphetoho e ka "baloa" ke liprotheine tse ling ho hlahisa litlamorao tse itseng tsa baeloji - mohlala, ho hira li-complex tsa activator tsa transcriptional, li-complex tsa repressor, kapa liprotheine tsa tokiso ea DNA.
Liphetoho tsa Histone li laoloa ke lihlopha tse tharo tsa liprotheine:
– Bangoli: dienzyme tse eketsang diphetoho (mohlala, HAT bakeng sa acetylation, HMT bakeng sa methylation)
– Lirabara: lienzyme tse tlosang liphetoho (mohlala, HDAC bakeng sa ho tlosa acetylation, demethylase)
– Babali: liprotheine tse lemohang liphetoho (mohlala, li-bromodomain li lemoha acetylation)
Ho nchafatsa chromatin: ho fetola li-nucleosome ho laola liphatsa tsa lefutso
Ntle le diphetoho tsa dikhemikhale, disele di boetse di na le di-complex tsa ho lokisa di-chromatin tse sebedisang matla a ATP ho fetola boemo kapa sebopeho sa di-nucleosome. Di-complex tsena di ka:
– Ho fetola di-nucleosome (ho thella) e le hore dibaka tse itseng tsa DNA di bulehe/di kwalwe
- Ho tlosa kapa ho nkela li-histone sebaka ka mefuta e fapaneng
– E laola sebaka se pakeng tsa li-nucleosome
Ho ntjhafatsa ke habohlokoa ha dijini di hloka ho kenngwa tshebetsong kapele, ha DNA e hloka ho phetwa, kapa ha tshenyo ya DNA e etsahala e hlokang phihlello ya dienzyme tse lokiswang.
Li-Histones, ho ikatisa ha DNA, le tokiso ea tšenyo
Ha lisele li ikatisa DNA, chromatin e tlameha ho qhaqhoa ka nakoana ka pel'a fereko ea ho ikatisa le ho kopanngoa hape ka mor'a eona. Li-histone tsa khale le tse ncha li abeloa DNA ea morali, li thusoa ke liprotheine tsa "chaperone" tsa histone. Ts'ebetso ena ha e akarelletse feela ho paka hape empa hape e kenyelletsa "mohopolo" oa taolo ea liphatsa tsa lefutso (mohlala, mekhoa ea phetoho ea histone) ho boloka boitsebiso bo tsitsitseng ba sele.
Tokisong ea tšenyo ea DNA, chromatin le eona e fetoha. Tšenyo e kang ho robeha ha likhoele tse peli e baka matšoao a fetolang li-histone tse itseng (mohlala, phosphorylation ea H2A.X ho li-eukaryote tse ngata) ho hira mechini ea tokiso. Ntle le liphetoho tsa chromatin, libaka tse ngata tsa DNA li thatafalloa ke li-enzyme tsa tokiso ho li fihlela.
Chromatin le epigenetics
Puisano ea li-histone hangata e kopana le li-epigenetics, e leng phetoho e futsitsoeng ea mekhoa ea tlhahiso ea liphatsa tsa lefutso ntle le ho fetola tatellano ea DNA. Liphetoho tsa histone, mefuta ea histone, le maemo a nucleosome li ka sebetsa e le matšoao a epigenetic. Hammoho le methylation ea DNA le RNA e sa ngoleng khoutu, sistimi ena e lumella lisele tse nang le DNA e tšoanang (mohlala, lisele tsa mesifa le lisele tsa methapo) ho ba le mananeo a fapaneng a liphatsa tsa lefutso.
Ho se laolehe hantle ha epigenetic ho ka kenya letsoho maemong a fapaneng, ho kenyeletsoa kankere, mathata a ntshetsopele, le mafu a methapo. Ka lebaka la ho fetoha ha tsona, dikarolo tsa epigenetic le tsona ke sepheo sa kalafo, tse kang dithibela-HDAC kapa dienzyme tse itseng tsa methylation, maemong a itseng a bongaka.
Ho koala
Li-histone le sebopeho sa chromatin ke metheo ea bohlokoa ea baeloji ea limolek'hule ea sejoale-joale. Li-histone ha se feela "li-wind" bakeng sa DNA, empa ke likarolo tsa taolo tse lumellang DNA ho kopanngoa ha e ntse e sebetsa. Ka ho thehoa ha nucleosome, ho hatelloa ho ntlafetseng, liphetoho tsa mohatla oa histone, mefuta ea histone, le ho nchafatsoa ho tsamaisoang ke ATP, lisele li ka laola hore na liphatsa tsa lefutso li buloa neng le hokae, hore na DNA e ikatisoa joang, le hore na tšenyo e lokisoa joang. Ka ho utloisisa matla a chromatin, re ka bona genome eseng e le mongolo o sa fetoheng, empa e le mongolo o hlophisitsoeng bocha kamehla—o buloang, o koetsoeng, le o hlophisoang—ho boloka bophelo ba sele bo hokahane.
