LRH1-driven transcription factor circuitry for hepatocyte identity: Super-enhancer cistromic analysis
DC Field | Value | Language |
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dc.contributor.author | Joo, Min Sung | - |
dc.contributor.author | Koo, Ja Hyun | - |
dc.contributor.author | Kim, Tae Hyun | - |
dc.contributor.author | Kim, Yun Seok | - |
dc.contributor.author | Kim, Sang Geon | - |
dc.date.accessioned | 2023-12-18T19:31:02Z | - |
dc.date.available | 2023-12-18T19:31:02Z | - |
dc.date.issued | 2019-02 | - |
dc.identifier.issn | 2352-3964 | - |
dc.identifier.issn | 2352-3964 | - |
dc.identifier.uri | https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/159355 | - |
dc.description.abstract | Background: The injured liver loses normal function, with concomitant decrease of key identity genes. Super-enhancers contribute to mammalian cell identity. Here, we identified core transcription factors (TFs) that are active in hepatocytes, using genome-wide analysis and hierarchical ordering of super-enhancer distribution. Methods: Expression of core TFs was assessed in a cohort of patients with hepatitis or cirrhosis and animal models. Quantitative PCR, chromatin immunoprecipitation assays, and hydrodynamic gene delivery methods were used to assess gene regulation and hepatocyte viability. RNA-sequencing data were generated to investigate the role of LRH1 in hepatocyte protection from injury. Results: Network analysis of super-enhancer-associated gene interactions and expression arrays for cohorts of patients with hepatitis and cirrhosis enabled us to identify a super-enhancer-associated network, and LRH1, HNF4α, PPARα, and RXRα as core TFs. In mouse models, expression of core TFs was robustly inhibited by single and multiple challenge(s) with liver toxicant. RNA-seq analysis revealed changes in expression in the super-enhancer-associated genes sensitively biased toward repression by intoxication. LRH1 gene delivery prevented the loss of hepatic super-enhancer-associated signaling circuitry in toxicant-challe | - |
dc.format.extent | 16 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Elsevier B.V. | - |
dc.title | LRH1-driven transcription factor circuitry for hepatocyte identity: Super-enhancer cistromic analysis | - |
dc.type | Article | - |
dc.publisher.location | 네델란드 | - |
dc.identifier.doi | 10.1016/j.ebiom.2018.12.056 | - |
dc.identifier.scopusid | 2-s2.0-85059653412 | - |
dc.identifier.wosid | 000460696900058 | - |
dc.identifier.bibliographicCitation | EBioMedicine, v.40, pp 488 - 503 | - |
dc.citation.title | EBioMedicine | - |
dc.citation.volume | 40 | - |
dc.citation.startPage | 488 | - |
dc.citation.endPage | 503 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S2352396418306339?via%3Dihub | - |
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