Hepatic DGAT2 gene expression is regulated by the synergistic action of ChREBP and SP1 in HepG2 cells
- Authors
- Shin, Eunji; Bae, Jin-Sik; Han, Jung-Youn; Lee, Junghoon; Jeong, Yun-Seung; Lee, Ho-Jae; Ahn, Yong-Ho; Cha, Ji-Young
- Issue Date
- 2-Jan-2016
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- DGAT2; ChREBP; SP1; triglyceride synthesis; transcriptional regulation
- Citation
- ANIMAL CELLS AND SYSTEMS, v.20, no.1, pp.7 - 14
- Journal Title
- ANIMAL CELLS AND SYSTEMS
- Volume
- 20
- Number
- 1
- Start Page
- 7
- End Page
- 14
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8668
- DOI
- 10.1080/19768354.2015.1131738
- ISSN
- 1976-8354
- Abstract
- Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride synthesis and plays a critical role in the development of fatty liver disease and insulin resistance. The expression of DGAT2 is mostly induced by dietary carbohydrate in the mammalian liver; however, the transcription factors that regulate DGAT2 expression have yet to be identified. In this study, we investigated the molecular mechanism underlying the glucose-induced transcriptional regulation of human DGAT2 in HepG2 cells. Human DGAT2 expression was increased by glucose in HepG2 cells. Transfection studies of the DGAT2 promoter-luciferase reporter construct in vitro and in silico analysis identified two glucose-responsive regions in the DGAT2 promoter. Each region contains one ChREBP/MLX (carbohydrate response element binding protein/Max-like protein) binding site (ChoRE, -539 to -551 and -6067 to -6083) and one specificity protein 1 (SP1) binding site (GC-rich motif, -556 to -572 and -6016 to -6032). Mutational analysis showed that both ChREBP/MLX and SP1 sites are required for the glucose-induced transcription of DGAT2. Gel shift assays and chromatin immunoprecipitation assays demonstrated that ChREBP and SP1 bind directly to ChoRE and the GC-rich motif, respectively. High glucose promoted the recruitment of ChREBP to ChoRE, whereas SP1 was recruited to the GC-rich motif even under low-glucose conditions. These data demonstrate that both ChREBP and SP1 are key factors to regulate the expression of human DGAT2 by glucose.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의예과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8668)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.