Methylation DNA na ngosipụta mkpụrụ ndụ ihe nketa
Methylation DNA bụ otu n'ime usoro epigenetic kachasị mkpa, na-achịkwa mgbe na otú mkpụrụ ndụ ihe nketa si egosipụta ike na-agbanweghị usoro ntọala DNA n'onwe ya. N'ikwu ya n'ụzọ ọzọ, ozi mkpụrụ ndụ ihe nketa ka dị otu, mana "agụmakwụkwọ" ya nwere ike ịgbanwe. Usoro a na-arụ ọrụ dị ukwuu na mmepe nwa ebu n'afọ, nhazi nke mkpụrụ ndụ ihe nketa, mmezi nke njirimara anụ ahụ, na ọbụna itinye aka ya na ọrịa dị iche iche dịka kansa. Ịghọta methylation DNA na-enyere anyị aka ịhụ na nhazi mkpụrụ ndụ ihe nketa abụghị naanị gbasara mkpụrụ ndụ ihe nketa anyị nwere, kamakwa otu esi "eme ka mkpụrụ ndụ ihe nketa ndị ahụ" rụọ ọrụ ma ọ bụ "gbachi nkịtị" n'ọnọdụ ndụ kpọmkwem.
Gịnị bụ DNA methylation?
Methylation DNA bụ mgbakwunye nke otu methyl (–CH₃) na molekul DNA. Na vertebrates, mgbanwe a na-emekarị na ntọala cytosine wee soro guanine (a na-akpọ saịtị CpG, site na "C-phosphate-G"). A pụrụ ime ka cytosine na saịtị CpG bụrụ methylated ka ọ bụrụ 5-methylcytosine (5mC). Ọ bụ ezie na ọ dị ka ọ dị mfe, mgbakwunye nke obere otu a nwere ike ịgbanwe mmekọrịta nke DNA na protein ndị na-achịkwa akwụkwọ, si otú a na-agbanwe ọkwa ngosipụta mkpụrụ ndụ ihe nketa.
Mkpụrụ ndụ DNA na-ada n'okpuru epigenetics n'ihi na a na-eketa ya n'oge nkewa mkpụrụ ndụ (mitosis) mana ọ na-agbanwe agbanwe ma ọ naghị agbanwe usoro nucleotide. Nke a pụtara na mkpụrụ ndụ abụọ nwere otu DNA ahụ—dịka ọmụmaatụ, mkpụrụ ndụ imeju na mkpụrụ ndụ akwara—nwere ike inwe ụdị methylation dị iche iche nke na-eme ka ha gosipụta ụdị mkpụrụ ndụ ihe nketa dị iche iche.
Enzymes ndị na-achịkwa methylation: DNMT
Usoro methylation anaghị eme n'onwe ya, kama ọ na-eduzi site na enzymes DNA methyltransferase (DNMT). N'ozuzu, enwere ọtụtụ DNMT dị mkpa:
1. DNMT3A na DNMT3B: bụ maka methylation de novo, ya bụ, nhazi nke usoro methylation ọhụrụ n'oge mmalite na mmepe nke mkpụrụ ndụ.
2. DNMT1: na-arụ ọrụ na mmezi methylation, ya bụ, ịnọgide na-enwe usoro methylation mgbe emechara DNA ka mkpụrụ ndụ nwa nwanyị wee keta "ncheta" epigenetic nke mkpụrụ ndụ nne na nna.
Mgbe DNA na-emegharị ọzọ, ụfọdụ methylation nwere ike "efu" n'ihi na eriri ọhụrụ ahụ enweghị methylation. DNMT1 na-amata DNA hemimethylated (eriri ochie ahụ bụ methylated, eriri ọhụrụ ahụ abụghị) ma na-agbakwụnye methyl na eriri ọhụrụ ahụ ka e wee nọgide na-enwe usoro methylation.
N'aka nke ọzọ, mwepụ methyl nwere ike ime site na usoro ndị na-adịghị arụ ọrụ (dịka ọmụmaatụ, ọdịda nke mmezi n'oge nkewa sel) ma ọ bụ site na enzymes dịka ezinụlọ TET (Ten-Eleven Translocation) nke na-eme ka oxidize 5mC ma na-akpali usoro ndozi DNA iji weghachi cytosins na-enweghị methylated.
Mmekọrịta dị n'etiti DNA methylation na ngosipụta mkpụrụ ndụ ihe nketa
Mmetụta nke methylation na ngosipụta mkpụrụ ndụ ihe nketa dabere na ebe methylation dị na genome.
1. Methylation na onye na-akwalite: na-eme ka mkpụrụ ndụ ihe nketa ghara ịdị jụụ
Onye nkwalite bụ mpaghara DNA dị nso na mmalite nke mkpụrụ ndụ ihe nketa nke na-arụ ọrụ dị ka "ebe mmalite" maka ntụgharị mkpụrụ ndụ ihe nketa. Ọtụtụ ndị na-akwalite mkpụrụ ndụ ihe nketa nwere nnukwu njupụta nke CpGs, nke a na-akpọ agwaetiti CpG. Ọ bụrụ na agwaetiti CpG dị na onye na-akwalite ya nwere methylation, ntụgharị mkpụrụ ndụ ihe nketa na-ebelata ma ọ bụ ọbụna kwụsị. Nke a na-eme site na usoro abụọ bụ isi:
– Na-egbochi ihe ndị na-egosi mgbanwe mkpụrụ ndụ ihe nketa: ụfọdụ ihe ndị na-egosi mgbanwe mkpụrụ ndụ ihe nketa enweghị ike ijikọ na DNA ma ọ bụrụ na ebe ndị a na-amata ha bụ methylated.
– Ịnweta protein ndị na-ejikọta methyl: Protein dịka MeCP2 nwere ike ịmata DNA methylated wee nweta ihe ndị na-egbochi nrụgide (dịka ọmụmaatụ, histone deacetylase/HDAC). N'ihi ya, chromatin na-aghọ obere (heterochromatin), igwe ntụgharị ahụ na-enwekwa nsogbu ịnweta mkpụrụ ndụ ihe nketa.
2. Methylation n'ime ahụ mkpụrụ ndụ ihe nketa: nwere ike imekọ ihe na mkpụrụ ndụ ihe nketa na-arụ ọrụ
N'ụzọ na-akpali mmasị, a na-ahụkarị methylation nke mkpụrụ ndụ ihe nketa na mkpụrụ ndụ ihe nketa ndị a na-egosipụta n'ọrụ. Otu echiche bụ na methylation nke mkpụrụ ndụ ihe nketa na-enyere aka igbochi mmalite ntụgharị "ebe a na-amaghị ama" ma na-eme ka ntụkwasị obi ntụgharị okwu ka mma. Ya mere, methylation abụghị ihe a na-ahụkarị mgbe niile na ịgbachi nkịtị; ihe dị na genomic dị mkpa.
3. Methylation nke ihe ndị na-eme ka ihe dịkwuo mma na ihe ndị ọzọ na-achịkwa
Ihe ndị na-eme ka mkpụrụ ndụ dịkwuo mma bụ ihe ndị nwere ike ime ka mkpụrụ ndụ dịkwuo mma. Methylation nke ihe ndị na-eme ka mkpụrụ ndụ dịkwuo mma na-ebelata ọrụ ihe ndị na-eme ka mkpụrụ ndụ dịkwuo mma, si otú a na-ebelata ngosipụta mkpụrụ ndụ ihe nketa ebumnuche. Mgbanwe na methylation nke ihe na-eme ka mkpụrụ ndụ dịkwuo mma nwere ike inye ụzọ ngwa ngwa maka mkpụrụ ndụ iji gbanwee mmemme mkpụrụ ndụ ihe nketa ha ka ọ dabara na mgbaàmà mmepe ma ọ bụ gburugburu ebe obibi.
Methylation DNA na mmepe na ọdịiche
N'oge mmepe nwa ebu n'afọ, nnukwu "nhazi" nke usoro methylation na-eme. N'oge ụfọdụ, methylation genomic na-ebelata n'ụwa niile, wee guzobe onwe ya ọzọ site na mgbanwe. Usoro a na-enye mkpụrụ ndụ ihe nketa embrayo ohere ịnọgide na-enwe mgbanwe, wee jiri nwayọọ nwayọọ mechie njirimara sel ha - dịka ọmụmaatụ, mkpụrụ ndụ akwara, mkpụrụ ndụ epithelial, ma ọ bụ neurons - site na imechi mkpụrụ ndụ ihe nketa ndị na-adịghị mkpa maka ọrụ ha.
Ihe atụ dị mfe: mkpụrụ ndụ ihe nketa dị mkpa na mkpụrụ ndụ akwara nwere ike ịdị na-arụ ọrụ n'ihi na ndị na-akwalite ha anaghị enwe methyl n'ime akwara, mana otu mkpụrụ ndụ ihe nketa ahụ nwere ike imechi mkpụrụ ndụ ihe nketa ahụ na mkpụrụ ndụ imeju site na methylation nke onye na-akwalite ya. Ya mere, methylation na-enyere aka ịnọgide na-enwe nkwụsi ike ogologo oge nke njirimara mkpụrụ ndụ.
Mbipụta mkpụrụ ndụ ihe nketa na mmechi nke kromozom X
Methylation DNA dịkwa mkpa na ihe omume epigenetic ụfọdụ:
– Mbipụta mkpụrụ ndụ ihe nketa bụ ngosipụta nke mkpụrụ ndụ ihe nketa dabere na nne na nna ha (nne ma ọ bụ nna). N'ime mkpụrụ ndụ ihe nketa ụfọdụ, a na-emechi otu mkpụrụ ndụ ihe nketa site na methylation, nke mere na naanị mkpụrụ ndụ ihe nketa nna ma ọ bụ nne na-egosipụta.
– Mbelata kromozom X n'ime anụmanụ ara bụ usoro nke ịkwụsị otu n'ime kromozom X iji mee ka nkesa mkpụrụ ndụ ihe nketa na nke ụmụ nwoke dị n'otu. Methylation na-arụ ọrụ n'ịnọgide na-enwe ọnọdụ a na-adịghị arụ ọrụ, yana mgbanwe histone na RNA na-abụghị koodu.
Usoro abụọ a na-egosi na methylation abụghị naanị ihe na-achịkwa nhazi nke ọma, kama ọ bụ usoro "mgbanwe" nke nwere ike ịmepụta usoro kwụsiri ike nke ngosipụta mkpụrụ ndụ ihe nketa.
Methylation DNA na ọrịa
Mgbanwe na usoro methylation nwere ike imebi iwu mkpụrụ ndụ ihe nketa ma tinye aka na ọrịa.
1. Ọrịa kansa
N'ọrịa kansa, ihe abụọ yiri ka ha na-emegiderịta onwe ha na-emekarị ọnụ:
– Hypomethylation zuru ụwa ọnụ: mbelata methylation n'ọtụtụ mpaghara nke genome nwere ike ibute enweghị ntụkwasị obi na genome, mkpali nke ihe ndị a na-agbanwe agbanwe, na mmụba nke mgbanwe.
– Mmepụta mkpụrụ ndụ ihe nketa nke na-egbochi etuto ahụ: Ndị na-akwalite mkpụrụ ndụ ihe nketa nke kwesịrị igbochi uto mkpụrụ ndụ nwere ike ịghọ ndị na-eme ka mkpụrụ ndụ ihe nketa ghara ịdị mma, na-emechi mkpụrụ ndụ ihe nketa ahụ. N'ihi ya, mkpụrụ ndụ nwere ike ịba ụba n'ụzọ na-enweghị njikwa.
Ebe ọ bụ na methylation nwere ike ịgbanwe agbanwe, ejirila ọgwụgwọ epigenetic dịka ndị na-egbochi DNMT n'ụdị ụfọdụ nke kansa iji gbalịa "ịmeghe" mkpụrụ ndụ ihe nketa mechiri emechi.
2. Nsogbu akwara na mmepe
Protein ndị na-ejikọta DNA dịka MeCP2 na-ejikọta ya na ọrụ akwara ozi; mgbanwe dị na MECP2 nwere ike ibute ọrịa Rett. Nke a na-egosi na nkọwa nke methylation dị mkpa dịka methylation n'onwe ya.
3. Mmetụta gburugburu ebe obibi na ụdị ndụ
Nri (dịka ọmụmaatụ, folate dị ka onye na-enye methyl), ikpughe ihe ndị na-emerụ ahụ, nrụgide, na ihe ndị ọzọ metụtara ndụ nwere ike imetụta ụkpụrụ methylation. Ọ bụ ezie na mmekọrịta na-akpata na mmetụta ya n'ime mmadụ na-abụkarị ihe mgbagwoju anya, ọtụtụ nnyocha na-egosi na gburugburu ebe obibi nwere ike ịhapụ "akara epigenetic" nke nwere ike imetụta ihe egwu ọrịa.
Kedu ka esi amụ banyere methylation DNA?
Nnyocha methylation DNA na-aga n'ihu ngwa ngwa site na teknụzụ nhazi usoro. Usoro ndị a ma ama gụnyere:
– Usoro Bisulfite: Ọgwụgwọ Bisulfite na-agbanwe cytosine na-enweghị methylated ka ọ bụrụ uracil, ebe 5mC ka dị ka cytosine. Site n'ịtụnyere nsonaazụ usoro, ndị nchọpụta nwere ike ịse ebe methylation dị na mkpebi dị elu.
– Usoro Methylation: na-atụ methylation na ọtụtụ narị puku ebe CpG dị ngwa ngwa ma dịkwa ọnụ ala.
– Nnyocha dabere na PCR nke a na-akpọ Methylation specific: bara uru maka ịnwale ọnọdụ methylation nke mkpụrụ ndụ ihe nketa ụfọdụ, dịka ọmụmaatụ na ọmụmụ ihe gbasara ọrịa kansa.
A na-ejikọ nsonaazụ nha methylation na data ngosipụta mkpụrụ ndụ ihe nketa (transcriptome) iji ghọta mmetụta ọrụ ha.
Mmechi
Methylation DNA bụ isi ihe dị mkpa na nhazi epigenetic nke na-emetụta ngosipụta mkpụrụ ndụ ihe nketa n'ọnọdụ ya: ọ na-egbochikarị mkpụrụ ndụ ihe nketa mgbe ọ na-eme na ndị na-akwalite ya, mana ọ nwere ike inwe ọrụ ndị ọzọ mgbe ọ na-eme na ahụ mkpụrụ ndụ ihe nketa ma ọ bụ mpaghara ndị na-eme ka ihe dịkwuo mma. Site na ọrụ nke enzymes DNMT na sistemụ demethylation, mkpụrụ ndụ nwere ike ịtọlite, idobe, ma gbanwee ụkpụrụ ngosipụta mkpụrụ ndụ ihe nketa dịka mkpa mmepe na nzaghachi gburugburu ebe obibi si dị. Mgbe usoro a mebiri, ihe egwu nke ọrịa - karịsịa kansa na nsogbu mmepe - nwere ike ịbawanye. N'ihi ọdịdị ya na-agbanwe agbanwe ma nwee ike ịgbanwe agbanwe, DNA methylation abụghị naanị isiokwu bụ isi na bayoloji molekul kamakwa ọ bụ ubi na-ekwe nkwa maka nchọpụta na ọgwụgwọ dabere na epigenetic.
Ọ bụrụ na ịchọrọ, enwere m ike ịgbanwe isiokwu a ka ọ bụrụ nke agụmakwụkwọ ka mma (na ntụaka na okwu teknụzụ ndị ọzọ) ma ọ bụ nke a ma ama maka ndị na-agụ akwụkwọ n'ozuzu.
