Qaab-dhismeedka Histones iyo Chromatin
Nucleus-ka unugga eukaryotic, DNA-du ma jirto "mawduuc" oo u harsan naftiisa. Haddii dhammaan DNA-da aadanaha la furi lahaa, waxay dhererkeedu noqon lahaa qiyaastii laba mitir, inkastoo xudunta ay tahay dhowr micrometer oo kaliya dhexroor. Si loogu habeeyo tiradan aadka u badan ee walxaha hidde-sidaha iyadoo loo heli karo hababka bayoolojiga ee muhiimka ah, unugyadu waxay leeyihiin nidaam baakad oo nadiif ah oo firfircoon. Nidaamkan waxaa loo yaqaan chromatin, qaybaha muhiimka ahna waa histones - borotiinno yaryar, oo si togan u shaqeeya sida spools-ka ku wareegsan ee DNA-da lagu dhejiyo. Fahmidda histones iyo qaab-dhismeedka chromatin waxay naga caawineysaa inaan sharaxno sida hiddo-sidayaasha loo shido ama loo damiyo, sida unugyadu u qaybsamaan, iyo sababta isbeddellada yaryar ee baakadaha DNA-da loogu xiri karo cudurka.
Waa maxay kromatin?
Chromatin waa isku-dhafan ka kooban DNA, borotiinno (badanaa histones), iyo tiro borotiinno aan histone ahayn iyo RNA la xiriira. Shaqada aasaasiga ah ee Chromatin ma aha oo kaliya inay xirto DNA laakiin sidoo kale inay nidaamiso helitaanka macluumaadka hidde-sidaha. Chromatin si adag ayaa loo xirxiri karaa ama si dabacsan ayaa loo xidhi karaa, xaaladdanina waxay saamaysaa in hiddo-sidayaasha qaarkood si fudud loo akhriyo (loo qoro) ama ay u muuqdaan inay aamusnaadaan.
Guud ahaan, waxaa jira laba nooc oo chromatin ah oo inta badan laga hadlo:
1. Euchromatin: qaab-dhismeed dabacsan, oo hodan ku ah hiddo-sideyaasha, iyo firfircooni badan oo qoraal ahaan ah.
2. Heterochromatin: qaab-dhismeed cufan, oo inta badan ka kooban taxane soo noqnoqda, guud ahaanna aan firfircoonayn qoraalka. Heterochromatin sidoo kale wuxuu door muhiim ah ka ciyaaraa ilaalinta xasilloonida hidde-sideyaasha, tusaale ahaan gobollada centromere iyo telomere.
Waa muhiim in la xoojiyo in euchromatin iyo heterochromatin aysan ahayn qaybo adag; chromatin wuu isbeddeli karaa iyadoo loo eegayo baahiyaha unugyada, marxaladda wareegga unugyada, iyo calaamadaha deegaanka.
Histones: borotiinada asaasiga ah ee xirma DNA-da
Histones waa borotiinno qani ku ah amino acids-ka togan sida lysine iyo arginine. Dalacaaddan togan waa muhiim sababtoo ah DNA-da si taban ayaa loogu dallacaa sababtoo ah kooxaha fosfate-ka ee laf-dhabarta. Isdhexgalka elektrostatic-ka ee u dhexeeya histones iyo DNA-da waxay gacan ka geystaan samaynta qaab-dhismeedka baakadaha deggan.
Histones-ka ugu muhiimsan waxaa loo qaybiyaa laba kooxood:
– Histones-ka asaasiga ah: H2A, H2B, H3, iyo H4. Afartan waxay sameeyaan "xudunta" uu ku wareegsan yahay DNA-da.
– Xididdada isku xidhka: ugu horreyn H1 (iyo noocyada kala duwan ee ay leedahay). Xididdadani waxay gacan ka geystaan xasilinta isku xirka DNA-da ee u dhexeeya nucleosomes-ka waxayna kor u qaadaan heerarka sare ee baakadaha.
Marka laga soo tago histones-ka "canonical", waxaa sidoo kale jira noocyo kala duwan oo histone ah (tusaale ahaan, H2A.Z, H3.3, CENP-A) oo beddeli kara histones-ka caadiga ah meelo gaar ah. Kala duwanaanshahani waxay bixiyaan sifooyin gaar ah oo ku saabsan chromatin, sida taageeridda kicinta hidda-wadaha, jawaab celinta dhaawaca DNA-da, ama aqoonsiga centromere-ka.
Nukliyeer: cutubka aasaasiga ah ee qaab-dhismeedka chromatin
Unugga qaab-dhismeedka ugu aasaasiga ah ee koromatin waa nucleosome. Nucleosome-ku wuxuu ka kooban yahay:
- octa-mer Hisstone: 2 × (H2A, H2B, H3, H4)
– DNA-da ayaa ku duuban octa-mer oo qiyaastii ah 147 lammaane saldhig (bp)
– DNA-da "Linker" oo dhererkeedu kala duwan yahay (badanaa qiyaastii 20-80 bp), taas oo isku xirta hal nukliyeosome kan xiga
Si loo isticmaalo isbarbardhig, DNA-du waxay la mid tahay xarig, halka nukliyeosoomyadu ay la mid yihiin kuul. Qaab-dhismeedkan waxaa badanaa loogu yeeraa "kuul-ku-samee-xarig" wuxuuna matalaa heerka bilowga ee baakadka.
Doorka nukliyoosomku ma aha mid farsamo ahaan fudud. Maadaama DNA-da ku duuban histones ay noqoto mid aan la heli karin, joogitaanka iyo booska nukliyoosomku waxay go'aamin karaan in arrimaha qoraalka iyo ensaymada kale ay ku xidhmi karaan DNA-da. Si kale haddii loo dhigo, nukliyoosomku waa "albaab" furi kara ama xiri kara marin u helidda hiddo-sideyaasha.
Heerarka baakadaha Chromatin
Ka dib heerka nucleosome-ka, chromatin-ka waa la sii adkeyn karaa. Caadi ahaan, buugaagta waxbarashada waxay qeexayaan baakadaha heerarka badan leh:
1. Helix labanlaab ah oo DNA ah (2 nm)
2. Faybarro Nukliyeer ah (qiyaastii 10-11 nm)
3. Faybar 30 nm ah (qaabka solenoid ama zig-zag; jiritaankiisa xaaladaha unugyada nool ayaa wali laga doodayaa, laakiin fikradda cufnaanta horumarsan ayaa weli khuseysa)
4. Domain-ka wareegga: Faybarrada chromatin waxay sameeyaan wareegyo ku xiran qaab-dhismeedka borotiinka ee xudunta.
5. Koromosoomyada Metaphase: qaabka ugu cufan inta lagu jiro qaybinta unugyada.
Gudaha xudunta, qaab-dhismeedka saddex-geesoodka ah ee chromatin waa mid aad u habaysan. Hiddo-sidayaasha firfircoon waxay u muuqdaan inay ku yaalliin jawiyo u habboon qorista qoraalka, halka gobollada aamusan lagu "ururin karo" meelo gaar ah. Ururkani wuxuu ka caawiyaa isku-dubbaridka muujinta hidda-wadaha si hufan.
Wax ka beddelka Histone iyo "koodka histone"
Qaybta ugu badan ee wax laga beddelay ee histone waa dabada histone, taas oo ah qaybta N-terminal ee ka soo baxda nucleosome-ka. Dabadani waxay mari kartaa isbeddello kala duwan oo ka dambeeya tarjumaadda, tusaale ahaan:
– Xawaaraha: badanaa lysine; waxay u janjeertaa inay yareyso heerka togan ee histones si xiriirka DNA-da uu u daciifo oo chromatin-ku uu u furnaado, badanaana lala xiriiriyo kicinta hidda-wadaha.
– Methylation: lysine ama arginine; saameyntu waxay ku xiran tahay goobta. Tusaale ahaan, methylation-ka H3K4 badanaa wuxuu la xiriiraa hiddo-wadeyaal firfircoon, halka H3K9 ama H3K27 badanaa lala xiriiriyo aamusnaanta.
– Phosphorylation: badanaa waxay la xiriirtaa jawaab celinta dhaawaca DNA-da iyo nidaaminta mitosis-ka.
- Ubiquitination iyo wax ka beddelka kale ee saameeya xasilloonida iyo isdhexgalka chromatin.
Ururinta qaababka wax-ka-beddelka waxaa badanaa loogu yeeraa "koodka histone," fikradda ah in isku-darka qaar ee wax-ka-beddelka ay "akhriyi karaan" borotiinno kale si ay u soo saaraan saameyn bayooloji oo gaar ah - tusaale ahaan, qorista isku-dhafka firfircoonida qoraalka, isku-dhafka cadaadiska, ama borotiinnada dayactirka DNA-da.
Wax-ka-beddelka histone waxaa nidaamiya saddex kooxood oo borotiinno ah:
– Qorayaasha: ensaymyada ku dara wax ka beddelka (tusaale ahaan HAT ee acetylation, HMT ee methylation)
– Tirtirayaasha: ensaymyada ka saara wax ka beddelka (tusaale ahaan HDAC ee deacetylation, demethylase)
– Akhristayaasha: borotiinada aqoonsada wax ka beddelka (tusaale ahaan, bromodomains waxay aqoonsadaan acetylation)
Dib-u-habaynta Chromatin: u wareejinta nukleosomes si loo xakameeyo hiddo-wadaha
Marka laga soo tago wax ka beddelka kiimikada, unugyadu waxay sidoo kale leeyihiin isku-dhafan dib-u-habeyn chromatin ah oo adeegsada tamarta ATP si ay u beddelaan booska ama halabuurka nucleosomes. Isku-dhafkan wuxuu noqon karaa:
– Beddelidda nukleosomes (simbiriirixan) si goobaha DNA-da qaarkood ay u furnaadaan/xirmaan
- Ka saarista ama beddelidda histones noocyo kala duwan
- Waxay nidaamisaa masaafada u dhaxaysa nukleosomes-ka
Dib-u-habayntu waa lama huraan marka hiddo-sidayaashu u baahan yihiin in si dhakhso ah loo hawlgeliyo, marka DNA-da loo baahan yahay in la nuqulo, ama marka burburka DNA-da uu dhaco oo u baahan helitaanka ensaymada dayactirka.
Histones, nuqulka DNA-da, iyo hagaajinta burburka
Marka unugyadu ay nuqul ka sameeyaan DNA-da, chromatin waa in si ku meel gaar ah loogu kala furfuraa horteeda fargeetada taranka oo dib loogu soo celiyaa gadaasheeda. Histone-yadii hore iyo kuwa cusubba waxaa loo qaybiyaa DNA-da gabadha, iyadoo ay caawinayaan borotiinnada "chaperone" ee histone. Hawshani waxay ku lug leedahay dib-u-baakayn kaliya laakiin sidoo kale ilaalinta "xusuusta" nidaaminta hiddaha (tusaale ahaan, qaababka wax-ka-beddelka histone) si loo ilaaliyo aqoonsiga unugyada oo deggan.
Dayactirka burburka DNA-da, chromatin sidoo kale waa mid firfircoon. Dhaawaca sida jabka laba-xariiqle wuxuu kiciyaa calaamado wax ka beddelaya histones gaar ah (tusaale ahaan, fosfoorasaytka H2A.X ee eukaryo badan) si loo qoro mishiinnada dayactirka. Haddii aan la beddelin chromatin, meelo badan oo DNA ah way adag tahay in ensaymada dayactirka la gaaro.
Chromatin iyo epigenetics-ka
Doodda ku saabsan histones waxay inta badan la jaanqaadaysaa epigenetics, taas oo ah isbeddelka dhaxalka ee qaababka muujinta hidda-wadaha iyada oo aan wax laga beddelin taxanaha DNA-da. Wax-ka-beddelka histone, kala duwanaanshaha histone, iyo boosaska nucleosome waxay u dhaqmi karaan sida calaamadaha epigenetic-ga. Iyadoo lala kaashanayo methylation-ka DNA-da iyo RNA-ga aan codayn, nidaamkani wuxuu u oggolaanayaa unugyada leh DNA-da isku midka ah (tusaale ahaan, unugyada murqaha iyo unugyada neerfaha) inay yeeshaan barnaamijyo hidde-side oo kala duwan.
Khalkhalka epigenetic-ga wuxuu gacan ka geysan karaa xaalado kala duwan, oo ay ku jiraan kansarka, cilladaha koritaanka, iyo cudurrada neerfaha. Sababtoo ah dib-u-noqoshadooda, qaybaha epigenetic-ga ayaa sidoo kale ah bartilmaameedyo daaweyn ah, sida inhibitors HDAC ama enzymes gaar ah oo methylation ah, xaalado caafimaad oo gaar ah.
Xiritaanka
Qaab-dhismeedka Histones iyo chromatin waa aasaaska muhiimka ah ee bayoolajiga casriga ah ee molecular-ka. Histones kaliya maaha "wareejiyeyaal" DNA-da, laakiin waa qaybo sharciyeed oo u oggolaanaya DNA-da in la isku ururiyo iyadoo sii shaqeyneysa. Iyada oo loo marayo sameynta nucleosome, isku-ururinta la xoojiyay, wax ka beddelka dabada histone, kala duwanaanshaha histone, iyo dib-u-habaynta ATP-ku wado, unugyadu waxay nidaamin karaan goorta iyo meesha hiddo-sideyaasha la shido, sida DNA-da loo soo celiyo, iyo sida dhaawaca loo hagaajiyo. Marka la fahmo dhaqdhaqaaqa chromatin, waxaan u arki karnaa genome-ka qoraal aan joogto ahayn, laakiin sida qoraal gacmeed si joogto ah dib loogu habeynayo - la furay, la xiray, oo wax laga beddelay - si loo ilaaliyo nolosha unugga isku xiran.
