Saccharomyces cerevisiae의 Swd2와 Set1의 결합이 Swd2의 이중적인 기능에 미치는 영향 = The effect of Swd2's binding to Set1 on the dual functions of Swd2 in Saccharomyces cerevisiae

국문 초록 (Abstract)

진핵 세포에서 히스톤의 변형은 크로마틴 구조를 조절하는 데에 있어서 중요한 메커니즘이다. Set1 복합체에 의한 히스톤 H3의 네 번째 라이신 잔기(H3K4)에 발생하는 메틸화는 다양하게 잘 알려져 있는 히스톤 변형 중 하나이다. Set1 complex는 H2B의 유비퀴틴화에 의존적으로 발생하는 H3K4 메틸화에 중요하다고 알려진 Swd2를 포함하여 7개의 소단위 단백질을 가지고 있다. Swd2는 Set1의 RNA recognition motif (RRM) 도메인 근처에 결합하여 Set1의 활성을 조절하고, 또 RNA의 3' 말단 형성에 관여하는 CPF (Cleavage and Polyadenylation Factors) 복합체의 구성성분이라고 보고되었다. 최근 보고들에 따르면, 이런 Swd2의 이중적인 기능이 서로 독립적으로 작용하며, Swd2 결실돌연변이 균주가 살지 못하는 이유가 CPF 복합체의 구성성분으로써의 기능 때문이라고 알려져 있다. 본 연구에서 우리는 Swd2가 Set1의 RRM 도메인에 결합하여 Set1의 활성을 조절할 수 있을 뿐만 아니라, Set1의 안정성에도 영향을 줄 수 있음을 발견하였다. 또 우리는 Swd2가 결합할 수 없는 truncated-Set1을 가지고 있는 ${\Delta}swd2$ 돌연변이가 사멸하지 않고 정상적으로 자라는 것을 관찰하였다. 이런 결과들은 Saccharomyces cerevisiae에서 H3K4 메틸화와 RNA 3' 말단 형성과정에서의 Swd2의 이중적인 기능이 서로 독립적인 것이 아님을 제안하다.

다국어 초록 (Multilingual Abstract)

In eukaryotic cells, histone modification is an important mechanism to regulate the chromatin structure. The methylation of the fourth lysine on histone H3 (H3K4) by Set1 complex is one of the various well-known histone modifications. Set1 complex has seven subunits including Swd2, which is known to be important for H2B ubiquitination dependent on H3K4 methylation. Swd2 was reported to regulate Set1's methyltransferase activity by binding to near RNA recognition motif (RRM) domain of Set1 and to act as a component of CPF (Cleavage and Polyadenylation Factors) complex involved in RNA 3' end processing. According to the recent reports, two functions of Swd2 work independently of each other and the lethality of Swd2 knockout strain was known to be caused by its function as a component of CPF complex. In this study, we found that Swd2 could influence the Set1's stability as well as histone methyltransferase activity through the association with RRM domain of Set1. Also, we found that ${\Delta}swd2$ mutant bearing truncated-Set1, which cannot interact with Swd2, lost its lethality and grew normally. These results suggest that the dual functions of Swd2 in H3K4 methylation and RNA 3' end processing are not independent in Saccharomyces cerevisiae.

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