Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 박장환 | - |
dc.date.accessioned | 2018-05-02T02:43:26Z | - |
dc.date.available | 2018-05-02T02:43:26Z | - |
dc.date.issued | 2014-02 | - |
dc.identifier.citation | Development, 2014, 141(4), P.761-772 | en_US |
dc.identifier.issn | 0950-1991 | - |
dc.identifier.uri | http://dev.biologists.org/content/141/4/761 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/71174 | - |
dc.description.abstract | Understanding how dopamine (DA) phenotypes are acquired in midbrain DA (mDA) neuron development is important for bioassays and cell replacement therapy for mDA neuron-associated disorders. Here, we demonstrate a feed-forward mechanism of mDA neuron development involving Nurr1 and Foxa2. Nurr1 acts as a transcription factor for DA phenotype gene expression. However, Nurr1-mediated DA gene expression was inactivated by forming a protein complex with CoREST, and then recruiting histone deacetylase 1 (Hdac1), an enzyme catalyzing histone deacetylation, to DA gene promoters. Coexpression of Nurr1 and Foxa2 was established in mDA neuron precursor cells by a positive cross-regulatory loop. In the presence of Foxa2, the Nurr1-CoREST interaction was diminished (by competitive formation of the Nurr1-Foxa2 activator complex), and CoRESTHdac1 proteins were less enriched in DA gene promoters. Consequently, histone 3 acetylation (H3Ac), which is responsible for open chromatin structures, was strikingly increased at DA phenotype gene promoters. These data establish the interplay of Nurr1 and Foxa2 as the crucial determinant for DA phenotype acquisition during mDA neuron development.도파민 (DA) 표현형이 중뇌 DA (mDA) 뉴런 개발에서 획득되는 이해는 마다 뉴런 연관 장애를 위해 생물학적 정량과 세포 교체 요법에 중요하다. 여기에서, 우리는 Nurr1과 Foxa2를 포함하여 마다 뉴런 개발의 사육-전진 메커니즘을 증명한다. Nurr1은 DA 표현형 유전자 발현을 위한 전사 인자의 역할을 한다. 그러나, Nurr1-개재된 DA 유전자 발현은 단백질 복합체를 코레스트로 형성시키고, 그리고 나서 DA 유전자 프로모터에게 히스톤 데아세틸라아제 1 (Hdac1), 효소 촉매작용화 히스톤 탈아세틸화를 보충함으로써 비활성화시켰다. Nurr1과 Foxa2의 동시 발현은 긍정적 교차 규제 루프에 의해 마다 뉴런 전구 세포에서 설치되었다. Foxa2의 면전에서, Nurr1-CoREST 상호작용은 감소시키 (Nurr1-Foxa2 활성제 복합체의 경쟁적 형성에 의해)과 CoREST-Hdac1 단백질이 DA 유전자 프로모터에 덜 풍부했다. 따라서, 열린 염색질 구조에 대한 책임이 있는 히스톤 3 아세틸화 (H3Ac)는 두드러지게 DA 표현형 유전자 프로모터에 증가되었다. 이러한 데이터는 마다 뉴런 개발 동안 Nurr1과 Foxa2 간의 상호 작용을 DA 표현형 획득을 위한 결정적 결정자로 확립한다. | en_US |
dc.description.sponsorship | This work was supported by grants from the Bio and Medical TechnologyDevelopment Program (2010-0020232) and the Medical Research Center (2008-0062190). S.-H.Y. was supported by the Basic Science Research Program(2012R1A6A3A01019699), funded by the National Research Foundation of Korea(NRF) of the Ministry of Education, Science and Technology (MEST), Republic of Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Company of Biologist LTD | en_US |
dc.subject | Foxa2 | en_US |
dc.subject | Nurr1 | en_US |
dc.subject | Midbrain dopamine neuron | en_US |
dc.subject | Development | en_US |
dc.subject | Neural precursor cell | en_US |
dc.subject | Epigenetic control | en_US |
dc.subject | CoREST | en_US |
dc.subject | Hdac | en_US |
dc.subject | Mouse | en_US |
dc.title | Foxa2 acts as a co-activator potentiating expression of the Nurr1-induced DA phenotype via epigenetic regulation | en_US |
dc.type | Article | en_US |
dc.relation.no | 4 | - |
dc.relation.volume | 141 | - |
dc.identifier.doi | 10.1242/dev.095802 | - |
dc.relation.page | 761-772 | - |
dc.relation.journal | DEVELOPMENT | - |
dc.contributor.googleauthor | Yi, Sang-Hoon | - |
dc.contributor.googleauthor | He, Xi-Biao | - |
dc.contributor.googleauthor | Rhee, Yong-Hee | - |
dc.contributor.googleauthor | Park, Chang-Hwan | - |
dc.contributor.googleauthor | Takizawa, Takumi | - |
dc.contributor.googleauthor | Nakashima, Kinichi | - |
dc.contributor.googleauthor | Lee, Sang-Hun | - |
dc.relation.code | 2014028314 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | chshpark | - |
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