Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster

Eungseok Kim, Shaozhen Xie, Shauh Der Yeh, Yi Fen Lee, Loretta L. Collins, Yueh Chiang Hu, Chih Rong Shyr, Xiao Min Mu, Ning Chun Liu, Yen Ta Chen, Peng Hui Wang, Chawnshang Chang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Apolipoprotein E (apoE) is synthesized in many tissues, and the liver is the primary site from which apoE redistributes cholesterol and other lipids to peripheral tissues. Here we demonstrate that the TR4 orphan nuclear receptor (TR4) can induce apoE expression in HepG2 cells. This TR4-mediated regulation of apoE gene expression was further confirmed in vivo using TR4 knockout mice. Both serum apoE protein and liver apoE mRNA levels were significantly reduced in TR4 knockout mice. Gel shift and luciferase reporter gene assays further demonstrated that TR4 can induce apoE gene expression via a TR4 response element located in the hepatic control region that is 15 kb downstream of the apoE gene. Furthermore our in vivo data from TR4 knockout mice prove that TR4 can also regulate apolipoprotein C-I and C-II gene expression via the TR4 response element within the hepatic control region. Together our data show that loss of TR4 down-regulates expression of the apoE/C-I/C-II gene cluster in liver cells, demonstrating important roles of TR4 in the modulation of lipoprotein metabolism.

Original languageEnglish
Pages (from-to)46919-46926
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number47
DOIs
Publication statusPublished - Nov 21 2003
Externally publishedYes

Fingerprint

Nuclear Receptor Subfamily 2, Group C, Member 2
Apolipoprotein C-I
Apolipoproteins E
Multigene Family
Liver
Genes
Gene expression
Knockout Mice
Response Elements
Gene Expression
Tissue
Hep G2 Cells
Luciferases
Reporter Genes
Metabolism
Lipoproteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster. / Kim, Eungseok; Xie, Shaozhen; Yeh, Shauh Der; Lee, Yi Fen; Collins, Loretta L.; Hu, Yueh Chiang; Shyr, Chih Rong; Mu, Xiao Min; Liu, Ning Chun; Chen, Yen Ta; Wang, Peng Hui; Chang, Chawnshang.

In: Journal of Biological Chemistry, Vol. 278, No. 47, 21.11.2003, p. 46919-46926.

Research output: Contribution to journalArticle

Kim, E, Xie, S, Yeh, SD, Lee, YF, Collins, LL, Hu, YC, Shyr, CR, Mu, XM, Liu, NC, Chen, YT, Wang, PH & Chang, C 2003, 'Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster', Journal of Biological Chemistry, vol. 278, no. 47, pp. 46919-46926. https://doi.org/10.1074/jbc.M304088200
Kim, Eungseok ; Xie, Shaozhen ; Yeh, Shauh Der ; Lee, Yi Fen ; Collins, Loretta L. ; Hu, Yueh Chiang ; Shyr, Chih Rong ; Mu, Xiao Min ; Liu, Ning Chun ; Chen, Yen Ta ; Wang, Peng Hui ; Chang, Chawnshang. / Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 47. pp. 46919-46926.
@article{7367eb7c3c6d4bc1b3aa423e2ab3a53e,
title = "Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster",
abstract = "Apolipoprotein E (apoE) is synthesized in many tissues, and the liver is the primary site from which apoE redistributes cholesterol and other lipids to peripheral tissues. Here we demonstrate that the TR4 orphan nuclear receptor (TR4) can induce apoE expression in HepG2 cells. This TR4-mediated regulation of apoE gene expression was further confirmed in vivo using TR4 knockout mice. Both serum apoE protein and liver apoE mRNA levels were significantly reduced in TR4 knockout mice. Gel shift and luciferase reporter gene assays further demonstrated that TR4 can induce apoE gene expression via a TR4 response element located in the hepatic control region that is 15 kb downstream of the apoE gene. Furthermore our in vivo data from TR4 knockout mice prove that TR4 can also regulate apolipoprotein C-I and C-II gene expression via the TR4 response element within the hepatic control region. Together our data show that loss of TR4 down-regulates expression of the apoE/C-I/C-II gene cluster in liver cells, demonstrating important roles of TR4 in the modulation of lipoprotein metabolism.",
author = "Eungseok Kim and Shaozhen Xie and Yeh, {Shauh Der} and Lee, {Yi Fen} and Collins, {Loretta L.} and Hu, {Yueh Chiang} and Shyr, {Chih Rong} and Mu, {Xiao Min} and Liu, {Ning Chun} and Chen, {Yen Ta} and Wang, {Peng Hui} and Chawnshang Chang",
year = "2003",
month = "11",
day = "21",
doi = "10.1074/jbc.M304088200",
language = "English",
volume = "278",
pages = "46919--46926",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "47",

}

TY - JOUR

T1 - Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster

AU - Kim, Eungseok

AU - Xie, Shaozhen

AU - Yeh, Shauh Der

AU - Lee, Yi Fen

AU - Collins, Loretta L.

AU - Hu, Yueh Chiang

AU - Shyr, Chih Rong

AU - Mu, Xiao Min

AU - Liu, Ning Chun

AU - Chen, Yen Ta

AU - Wang, Peng Hui

AU - Chang, Chawnshang

PY - 2003/11/21

Y1 - 2003/11/21

N2 - Apolipoprotein E (apoE) is synthesized in many tissues, and the liver is the primary site from which apoE redistributes cholesterol and other lipids to peripheral tissues. Here we demonstrate that the TR4 orphan nuclear receptor (TR4) can induce apoE expression in HepG2 cells. This TR4-mediated regulation of apoE gene expression was further confirmed in vivo using TR4 knockout mice. Both serum apoE protein and liver apoE mRNA levels were significantly reduced in TR4 knockout mice. Gel shift and luciferase reporter gene assays further demonstrated that TR4 can induce apoE gene expression via a TR4 response element located in the hepatic control region that is 15 kb downstream of the apoE gene. Furthermore our in vivo data from TR4 knockout mice prove that TR4 can also regulate apolipoprotein C-I and C-II gene expression via the TR4 response element within the hepatic control region. Together our data show that loss of TR4 down-regulates expression of the apoE/C-I/C-II gene cluster in liver cells, demonstrating important roles of TR4 in the modulation of lipoprotein metabolism.

AB - Apolipoprotein E (apoE) is synthesized in many tissues, and the liver is the primary site from which apoE redistributes cholesterol and other lipids to peripheral tissues. Here we demonstrate that the TR4 orphan nuclear receptor (TR4) can induce apoE expression in HepG2 cells. This TR4-mediated regulation of apoE gene expression was further confirmed in vivo using TR4 knockout mice. Both serum apoE protein and liver apoE mRNA levels were significantly reduced in TR4 knockout mice. Gel shift and luciferase reporter gene assays further demonstrated that TR4 can induce apoE gene expression via a TR4 response element located in the hepatic control region that is 15 kb downstream of the apoE gene. Furthermore our in vivo data from TR4 knockout mice prove that TR4 can also regulate apolipoprotein C-I and C-II gene expression via the TR4 response element within the hepatic control region. Together our data show that loss of TR4 down-regulates expression of the apoE/C-I/C-II gene cluster in liver cells, demonstrating important roles of TR4 in the modulation of lipoprotein metabolism.

UR - http://www.scopus.com/inward/record.url?scp=10744222805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744222805&partnerID=8YFLogxK

U2 - 10.1074/jbc.M304088200

DO - 10.1074/jbc.M304088200

M3 - Article

C2 - 12954636

AN - SCOPUS:10744222805

VL - 278

SP - 46919

EP - 46926

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 47

ER -