DNMT1
DNMT1
DNA (시토신-5)-메틸전달효소 1은 DNA 메틸화라고 불리는 과정인 DNA의 특정 CpG 구조로의 메틸기 전달을 촉매하는 효소이다.인간에서는 DNMT1 [5]유전자에 의해 암호화된다.DNMT1은 주로 DNMT1, DNMT3A 및 DNMT3B로 구성된 DNA 메틸전달효소군의 일부를 형성한다.
기능.
이 효소는 DNA 메틸화를 유지하는데 책임이 있으며, 이것은 세포 분열에 걸쳐 후생유전 패턴의 충실도를 보장합니다.이러한 역할과 함께, 반메틸화 [6]DNA에서 CpGs를 메틸화하는 것을 강하게 선호한다.그러나 Dnmt1은 트랜스포저블 요소 및 부계 임프린트 제어 [7][8]영역을 포함한 특정 게놈 컨텍스트에서 de novo DNA 메틸화를 촉매할 수 있다.비정상적인 메틸화 패턴은 특정 인간 종양 및 발달 [9][10]이상과 관련이 있다.
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상호 작용
DNMT1은 UHRF1과 상호작용하는 것으로 나타났습니다.
DNMT1은 세포주기의 S상 동안 딸 DNA [18]가닥에서 새롭게 생성된 반메틸화 부위의 메틸화에 필요할 때 고도로 전사된다.PCNA 및 UHRF1과의 상호작용에 의해 리플리케이션포크로 [19]현지화됩니다.DNMT1과 G9a 사이의 직접적인 협력은 세포 [17]분열 중 DNA와 H3K9 메틸화를 조정한다.이 염색질 메틸화는 포유류의 발달 과정에서 유전자 발현을 안정적으로 억제하기 위해 필요하다.
모델 유기체
녹아웃 실험은 이 효소가 마우스 세포에서 메틸화의 대부분을 담당하며 배아 [20]발달에 필수적이라는 것을 보여주었다.또한 모체 및 접합체 Dnmt1의 부족은 배반포에서 [21]각인된 유전자의 완전한 탈메틸화를 초래하는 것으로 나타났다.
임상적 의의
DNMT1은 조혈줄기세포(HSC) 유지에 중요한 역할을 한다.DNMT1이 감소된 HSC는 이식 [22]후 효율적으로 자가 재생되지 않는다.그것은 또한 장내줄기세포와 유방줄기세포와 같은 다른 종류의 줄기세포에도 중요한 것으로 나타났다.DNMT1을 조건부로 삭제하면 장 전체의 저메틸화, ISC의 크립트 확장 및 분화 타이밍 변경, MaaS의 [23]증식 및 유지 등이 발생한다.
레퍼런스
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추가 정보
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