Iimveliso

I-Tet 5-methylcytosine dioxygenases yenza i-DNA demethylation ngokuvelisa i-5-hydroxymethylcytosine kunye neemveliso ezingaphezulu kwe-oxidized.I-Tet1 kunye ne-Tet2 zibonakaliswe kakhulu kwiiseli ze-pluripotent ze-mouse kwaye zithotywe kwimilinganiselo eyahlukeneyo kwiiseli ze-somatic, kodwa iindlela zokubhaliweyo azicacanga.Apha sichaze imimandla yokukhuthaza kunye nesixhasi kwiTet1 kunye neTet2.Ngaphakathi kwe-15-kb ye-"superenhancer" ye-Tet1, kukho iisayithi ezimbini zokuqalisa ukukhutshelwa (TSSs) ezineepateni zokuvula ezahlukeneyo ngexesha lophuhliso.Umgqugquzeli we-6-kb ummandla onyukayo we-TSS ye-distal usebenza kakhulu kwiiseli ze-pluripotent ezingenangqondo, ingxelo ngokuzimeleyo i-Tet1 ibonakaliso kwinkqubo ye-transgenic, kwaye ihamba ngokukhawuleza i-DNA methylation kunye nokuthuliswa ekuhlukeni kweeseli ezikhuliswe kunye ne-epiblast yasekhaya.I-TSS yesibini emazantsi omlambo, eyayanyaniswa nomkhuthazi obuthathaka ngokwe-CpG-esityebi, yenziwa yasebenza sisixhasi esingummelwane kwiiseli ze-embryonic stem (ESCs) kunye neeseli ze-epiblast-ezifana ne-primed (EpiLCs).I-Tet2 ine-promoter yesiqithi se-CpG esinomsebenzi ozimeleyo we-pluripotency kunye ne-ESC-specific distal intragenic enhancer;le yokugqibela ithotywa ngokukhawuleza kwii-EpiLCs.Uphononongo lwethu lubonisa iindlela ezahlukeneyo zolawulo lokukhutshelwa kwi-Tet1 kunye ne-Tet2 ngexesha lokutshintsha kweeseli zophuhliso lwangaphambili.Iintatheli ezitsha ze-transgenic ezisebenzisa i-Tet1 kunye ne-Tet2 i-cis-regulatory domains inokusebenza ukwahlula utshintsho oluncinci kwi-pluripotent states kunye nokwahluka kwe-epigenetic.