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김영채 (Young-Chae Kim) 저자 이메일 보기
University of Illinois at Urbana-Champaign
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Liver ChIP-seq analysis in FGF19-treated mice reveals SHP as a global transcriptional partner of SREBP-2
Young-Chae Kim1†, Sangwon Byun1†, Yang Zhang2†, Sunmi Seok1, Byron Kemper1, Jian Ma23* and Jongsook Kim Kemper1*

1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana 61801, IL, USA 
2 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana 61801, IL, USA 
3 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana 61801, IL, USA 

* Corresponding authors: Jian Ma, Jongsook K Kemper
Equal contributors

Abstract

Background
Fibroblast growth factor-19 (FGF19) is an intestinal hormone that mediates postprandial metabolic responses in the liver. The unusual orphan nuclear receptor, small heterodimer partner (SHP), acts as a co-repressor for many transcriptional factors and has been implicated in diverse biological pathways including FGF19-mediated repression of bile acid synthesis. To explore global functions of SHP in mediating FGF19 action, we identify genome-wide SHP binding sites in hepatic chromatin in mice treated with vehicle or FGF19 by ChIP-seq analysis. 

Results
The overall pattern of SHP binding sites between these two groups is similar, but SHP binding is enhanced at the sites by addition of FGF19. SHP binding is detected preferentially in promoter regions that are enriched in motifs for unexpected non-nuclear receptors. We observe global co-localization of SHP sites with published sites for SREBP-2, a master transcriptional activator of cholesterol biosynthesis. FGF19 increases functional interaction between endogenous SHP and SREBP-2 and inhibits SREBP-2 target genes, and these effects were blunted in SHP-knockout mice. Furthermore, FGF19-induced phosphorylation of SHP at Thr-55 is shown to be important for its functional interaction with SREBP-2 and reduction of liver/serum cholesterol levels. 

Conclusion
This study reveals SHP as a global transcriptional partner of SREBP-2 in regulation of sterol biosynthetic gene networks and provides a potential mechanism for cholesterol-lowering action of FGF19. 

Keywords: FGF15; Bile acid; Nuclear receptor; HMGCR; Cholesterol biosynthesis
논문정보
- 형식: Research article
- 게재일: 2015년 12월 (BRIC 등록일 2015-12-08)
- 연구진: 국외연구진
- 분야: Biotechnology, Genetics
광유전학의 과거, 현재와 미래[Neuron]
김윤석
발표: 김윤석 (Stanford University)
일자: 2020년 7월 30일 (목) 오후 02시 (한국시간)
언어: 한국어
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