Histones uye Chimiro cheChromatin
Mukati memasero eeukaryotic, DNA haipo se "shinda" inosiyiwa yega. Dai DNA yese yemunhu yakavhurwa, yaizoreba mamita maviri, kunyangwe dhayamita yacho iri ma micrometer mashoma. Kuti ikwane huwandu hwakawanda hwezvinhu zvemajini uku ichiramba iri nyore kushandisa muzvinhu zvakakosha zvehupenyu, masero ane sisitimu yekurongedza yakatsetseka uye inochinja-chinja. Sisitimu iyi inozivikanwa sechromatin, uye zvikamu zvayo zvikuru mahistones—mapuroteni madiki, ane chaji yakanaka anoshanda semaspools akatenderedza iyo DNA yakavharirwa. Kunzwisisa mahistones nemaumbirwo echromatin kunotibatsira kutsanangura kuti majini anovhurwa kana kudzimwa sei, kuti masero anopatsanurwa sei, uye nei shanduko diki mumapakeji eDNA dzichigona kusanganiswa nechirwere.
Chii chinonzi chromatin?
Chromatin chinhu chakasanganiswa chine DNA, mapuroteni (kunyanya histones), uye mapuroteni asiri histone uye RNA yakabatana nayo. Basa guru reChromatin harisi rekungorongedza DNA chete asiwo kudzora mukana wekuwana ruzivo rwemajini. Chromatin inogona kusungirirwa zvakanyanya kana kusungirirwa zvisina kusimba, uye mamiriro aya anokanganisa kana mamwe majini achiverengwa zviri nyore (anonyorwa) kana kuti anowanzo ramba akanyarara.
Kazhinji, kune marudzi maviri echromatin anowanzo kurukurwa:
1. Euchromatin: chimiro chisina kusimba, majini akawanda, uye chinoshanda zvakanyanya pakunyorwa kwemasero.
2. Heterochromatin: chimiro chakakora, chinowanzova nezvikamu zvinodzokororwa, uye kazhinji hachina simba rekunyora. Heterochromatin inoitawo basa rakakosha mukuchengetedza kugadzikana kwemajini, semuenzaniso munzvimbo dze centromere ne telomere.
Zvakakosha kusimbisa kuti euchromatin neheterochromatin hazvisi zvikamu zvakasimba; chromatin inogona kuchinja zvichienderana nezvinodiwa nemasero, danho rekutenderera kwemasero, uye zviratidzo zvezvakatipoteredza.
Histones: mapuroteni makuru anotakura DNA
MaHistones mapuroteni akapfuma mumaamino acids ane positive charge akadai selysine nearginine. Iyi positive charge yakakosha nekuti DNA ine negative charge nekuda kwemapoka ephosphate ari mumusana wayo. Kudyidzana kwemaelectrostatic pakati pehistones neDNA kunobatsira kuumba chimiro chepurasitiki chakasimba.
Ma histones makuru akakamurwa kuita mapoka maviri:
– Macore histones: H2A, H2B, H3, uye H4. Aya mana anoumba "core" iyo DNA yakakomberedzwa.
– Linker histones: kunyanya H1 (nemhando dzayo). Aya mahistones anobatsira kudzikamisa hukama hweDNA pakati pemanucleosomes uye kukurudzira huwandu hwakakwira hwekurongedza.
Kuwedzera kune "canonical histones", kunewo mamwe marudzi ehistone (semuenzaniso, H2A.Z, H3.3, CENP-A) anogona kutsiva mahistones akajairwa panzvimbo dzakatarwa. Aya marudzi anopa hunhu hwakasiyana pachromatin, hwakadai sekutsigira gene activation, DNA damage response, kana centromere identity.
Nucleosome: chinhu chikuru chechimiro chechromatin
Chimiro chikuru che chromatin i nucleosome. Nucleosome ine:
-Histone octa-mer: 2 × (H2A, H2B, H3, H4)
– DNA yakaputirwa pa octa-mer ine ma base pairs angangoita 147 (bp)
– DNA ye "Linker" ine urefu hwakasiyana (kazhinji inenge 20–80 bp), iyo inobatanidza nucleosome imwe kune imwe
Kana tichienzanisa, DNA yakaita setambo, nepo nucleosome yakaita semabhedha. Chimiro ichi chinowanzonzi "mabhedha-pa-tambo" uye chinomiririra chiyero chekutanga chekurongedza.
Basa remanucleosome harisi remakanika chete. Nekuti DNA yakapoteredzwa nehistones inova isingawanikwe zvakanyanya, kuvapo nenzvimbo yemanucleosomes kunogona kuona kana transcription factors nemamwe maenzymes zvichigona kubatana neDNA. Nemamwe mashoko, manucleosomes "magedhi" anogona kuvhura kana kuvhara mukana wekuwana majini.
Mazinga ekurongedza eChromatin
Mushure mechikamu chenucleosome, chromatin inogona kuomeswa zvakanyanya. Kazhinji, mabhuku ekudzidzisa anotsanangura kurongedza kwemazinga akawanda:
1. DNA ine denderedzwa repiri remuchadenga (2 nm)
2. Nyuzi dzeNucleosome (inenge 10–11 nm)
3. 30 nm fiber (solenoid kana zig-zag model; kuvapo kwayo mumamiriro ezvinhu emasero mapenyu kuchiri kukurukurwa, asi pfungwa yekuwedzera kwesimba inoramba yakakosha)
4. Nzvimbo yeLoop: chromatin fibers dzinoumba zvishwe zvakasungirirwa pa protein framework iri mu nucleus.
5. Machromosome eMetaphase: chimiro chakanyanya kukora panguva yekupatsanurwa kwemasero.
Mukati menucleus, kurongeka kwechromatin muzvikamu zvitatu kwakarongwa zvakanaka. Majini anoshanda anowanzo kuwanikwa munzvimbo dzinoshanda kuti anyorerwe, nepo nzvimbo dzakanyarara dzichigona "kuunganidzwa" munzvimbo dzakatarwa. Kurongeka uku kunobatsira kuronga kugadzirwa kwemajini zvinobudirira.
Kugadziriswa kweHistone uye "histone code"
Chikamu chinonyanya kuchinjwa chehistone muswe wehistone, unova chikamu cheN-terminal chinobuda mu nucleosome. Muswe uyu unogona kugadziriswa zvakasiyana-siyana mushure mekushandurwa, semuenzaniso:
– Acetylation: kazhinji pa lysine; inowanzo kuderedza simba re histones zvekuti kubatana neDNA kunoderera uye chromatin inova yakavhurika zvakanyanya, kazhinji inobatanidzwa nekushandiswa kwemajini.
– Methylation: pa lysine kana arginine; mhedzisiro yacho inoenderana nenzvimbo. Semuenzaniso, methylation paH3K4 inowanzobatanidzwa nemajini anoshanda, nepo H3K9 kana H3K27 inowanzobatanidzwa nekunyarara.
– Phosphorylation: inowanzobatanidzwa nemhinduro yekukuvara kweDNA uye kutonga kwe mitosis.
- Ubiquitination nedzimwe shanduko dzinokanganisa kugadzikana kwechromatin uye kudyidzana.
Muunganidzwa uyu wemaitiro ekuchinja unowanzonzi "histone code," pfungwa iri yekuti mimwe misanganiswa yekuchinja inogona "kuverengwa" nemamwe mapuroteni kuti ibudise mhedzisiro chaiyo yehupenyu - semuenzaniso, kutsvaga ma complexes e transcriptional activator, ma repressor complexes, kana mapuroteni ekugadzirisa DNA.
Kugadziriswa kweHistone kunodzorwa nemapoka matatu emapuroteni:
– Vanyori: ma enzyme anowedzera shanduko (semuenzaniso HAT ye acetylation, HMT ye methylation)
– Zvirabha: ma enzyme anobvisa shanduko (semuenzaniso HDAC yekubvisa acetylation, demethylase)
- Vaverengi: mapuroteni anoziva shanduko (semuenzaniso, mabromodomains anoziva acetylation)
Kugadziriswazve kweChromatin: kushandura manucleosomes kuti agadzirise majini
Pamusoro pekuchinja kwemakemikari, masero anewo ma chromatin remodeling complexes anoshandisa simba reATP kushandura nzvimbo kana kuumbwa kwe nucleosomes. Ma complexes aya anogona:
- Kuchinja manucleosome (kutsvedza) kuitira kuti dzimwe nzvimbo dzeDNA dzivhurwe/dzivharwe
- Kubvisa kana kutsiva ma histones nemarudzi akasiyana
- Inodzora daro riri pakati pemanucleosome
Kugadzirisa kwakakosha kana majini achida kuvhurwa nekukurumidza, kana DNA ichida kudzokororwa, kana kana DNA ikakuvara iyo inoda kuti ma enzymes agadziriswe.
Histones, DNA replication, uye kukuvara kugadziriswa
Masero paanoita DNA yakafanana, chromatin inofanira kupatsanurwa kwenguva pfupi pamberi peforogo yekudzokorodza uye kuunganidzwazve kumashure kwayo. Ma histone ekare neatsva anogoverwa kuDNA mwanasikana, achibatsirwa nemapuroteni e "chaperone" e histone. Maitiro aya haangosanganisiri kungorongedza chete asiwo kuchengetedza "kurangarira" kwekutonga kwemajini (semuenzaniso, maitiro ekuchinja histone) kuchengetedza kuzivikanwa kwemasero kwakasimba.
Mukugadzirisa kukuvara kweDNA, chromatin inoshandukawo. Kukuvara kwakadai sekupwanyika kwetambo mbiri kunokonzera zviratidzo zvinoshandura ma histones chaiwo (semuenzaniso, phosphorylation yeH2A.X muma eukaryotes mazhinji) kuti iwane michina yekugadzirisa. Pasina shanduko dzechromatin, nzvimbo dzakawanda dzeDNA dzakaoma kusvika kuma enzymes ekugadzirisa.
Chromatin uye epigenetics
Kukurukurirana nezve histones kunowanzoenderana ne epigenetics, inova shanduko inowanikwa kubva mukugadzirwa kwemagene expression patterns pasina kuchinja DNA sequence. Kugadziriswa kwehistone, histone variants, uye nucleosome positions zvinogona kushanda se epigenetic markers. Pamwe chete neDNA methylation uye non-coding RNA, iyi system inobvumira masero ane DNA imwechete (semuenzaniso, masero emhasuru nemasero etsinga) kuti ave nemagene program akasiyana.
Kusarongeka zvakanaka kwe epigenetic kunogona kukonzera zvirwere zvakasiyana-siyana, zvinosanganisira kenza, matambudziko ekukura, uye zvirwere zvinokanganisa mashandiro etsinga. Nekuda kwekugona kwazvo kudzoka, zvikamu zve epigenetic zvinoshandiswawo pakurapa, senge HDAC inhibitors kana ma enzymes chaiwo e methylation, mune mamwe mamiriro ekiriniki.
Penutup
MaHistone nemaumbirwo echromatin ndiwo hwaro hwakakosha hwebiology yemazuva ano yemamorekuru. MaHistone haasi kungo "peta" DNA, asi ari zvinhu zvinodzora zvinobvumira DNA kuti iome ichiramba ichishanda. Kuburikidza nekuumbwa kwenucleosome, kuomeswa kwakawedzerwa, kugadziriswa kwemuswe wehistone, mavandudziro ehistone, uye kugadziriswa kweATP, masero anogona kudzora nguva uye kupi majini anovhurwa, kuti DNA inodzokororwa sei, uye kuti kukuvara kunogadziriswa sei. Nekunzwisisa chromatin dynamics, tinogona kuona genome kwete sechinyorwa chisingachinji, asi sechinyorwa chinogara chichigadziriswazve—chinovhurwa, chinovharwa, uye chinogadziriswa—kuti hupenyu hwesero hurambe hwakarongeka.
