Histone Lysine Methylation

국문 초록 (Abstract)

유핵세포의 게놈(genome)은 단백-DNA복합체인 염색질(chromatin)의 형태로 존재하는데, 생명현상을 유지하기 위해서는 생명체 또는 세포가 처한 상황에 맞게 염색질의 구조를 변화시키는 역동적인 조절기전이 필요하다. 염색질을 구성하는 기본단위는 히스톤 8량체 (histone octamer)를 포함하는 뉴클레오좀(nucleosome)이다. 히스톤 단백에는 여러 종류의 공유결합성 수식이 일어나는데, 그 중 하나가 라이신 잔기(lysine residue)에 일어나는 메틸화이다. 최근 수년간의 연구로 여러 개의 히스톤 라이신 메틸화효소(histone lysine methyltransferase, HKMT), 이에 결합하는 염색질단백 및 메틸화와 관련된 후생유전학적 현상이 밝혀졌으며, 특히 정밀한 연구방법을 동원한 다방면의 실험을 통하여 비록 자세한 기전과 전체적인 윤곽의 규명은 미흡하더라도 라이신 메틸화가 후생유전학적 변화를 초래하는 일부 과정이 규명 되었다. 또한 여러 종류의 라이신 탈메틸화효소가 최근에 발견됨에 따라, 아세틸화, 인산화등 다른 공유결합성 수식보다는 상대 적으로 안정되더라도, 히스톤 메 틸화로 유발되는 후생유전학적 변화가 불가역성이 아님을 알게 되었다.

다국어 초록 (Multilingual Abstract)

Our genome exists in the form of chromatin, and its structural organization should be precisely regulated with an appropriate dynamic nature for life. The basic unit of chromatin is a nucleosome, which consists of a histone octamer. These nucleosomal histones are subject to various covalent modifications, one of which is methylation on certain lysine residues. Recent studies in histone biology identified many histone Iysine methyltransferases (HKMTs) responsible for respective lysine residues and uncovered various kinds of involved chromatin associating proteins and many related epigenetic phenotypes. With the aid of highly precise experimental tools, multi-disciplinary approaches have widened our understanding of how lysine methylation functions in diverse epigenetic processes though detailed mechanisms remain elusive. Still being considered as a relatively more stable mark than other modifications, the recent discovery of lysine demethylases will confer more flexibility on epigenetic memory transmitted through histone lysine methylation. In this review, advances that have been recently observed in epigenetic phenotypes related with histone lysine methylation and the enzymes for depositing and removing the methyl mark are provided.

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