Intestinal apolipoprotein A-IV gene transcription is controlled by two hormone-responsive elements:: A role for hepatic nuclear factor-4 isoforms

被引:24
作者
Archer, A [1 ]
Sauvaget, D [1 ]
Chauffeton, V [1 ]
Bouchet, PE [1 ]
Chambaz, J [1 ]
Pinçon-Raymond, M [1 ]
Cardot, P [1 ]
Ribeiro, A [1 ]
Lacasa, M [1 ]
机构
[1] Univ Paris 06, INSERM, UMR 505, F-75006 Paris, France
关键词
D O I
10.1210/me.2004-0462
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4 alpha and gamma. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4 alpha repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4 alpha and gamma functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts.
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页码:2320 / 2334
页数:15
相关论文
共 59 条
[11]   EXPRESSION OF TRANSCRIPTION FACTOR HNF-4 IN THE EXTRAEMBRYONIC ENDODERM, GUT, AND NEPHROGENIC TISSUE OF THE DEVELOPING MOUSE EMBRYO - HNF-4 IS A MARKER FOR PRIMARY ENDODERM IN THE IMPLANTING BLASTOCYST [J].
DUNCAN, SA ;
MANOVA, K ;
CHEN, WS ;
HOODLESS, P ;
WEINSTEIN, DC ;
BACHVAROVA, RF ;
DARNELL, JE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7598-7602
[12]  
Duncan SA, 1997, DEVELOPMENT, V124, P279
[13]   EXPRESSION OF RAT APOLIPOPROTEIN-A-IV AND APOLIPOPROTEIN-A-I GENES - MESSENGER-RNA INDUCTION DURING DEVELOPMENT AND IN RESPONSE TO GLUCOCORTICOIDS AND INSULIN [J].
ELSHOURBAGY, NA ;
BOGUSKI, MS ;
LIAO, WSL ;
JEFFERSON, LS ;
GORDON, JI ;
TAYLOR, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (23) :8242-8246
[14]   Plasma distribution of apoA-IV in patients with coronary artery disease and healthy controls [J].
Ezeh, B ;
Haiman, M ;
Alber, HF ;
Kunz, B ;
Paulweber, B ;
Lingenhel, A ;
Kraft, HG ;
Weidinger, F ;
Pachinger, O ;
Dieplinger, H ;
Kronenberg, F .
JOURNAL OF LIPID RESEARCH, 2003, 44 (08) :1523-1529
[15]   A LOW-TEMPERATURE METHOD FOR THE ISOLATION OF SMALL-INTESTINAL EPITHELIUM ALONG THE CRYPT-VILLUS AXIS [J].
FLINT, N ;
COVE, FL ;
EVANS, GS .
BIOCHEMICAL JOURNAL, 1991, 280 :331-334
[16]   Distinct functions are implicated for the GATA-4, -5, and -6 transcription factors in the regulation of intestine epithelial cell differentiation [J].
Gao, XP ;
Sedgwick, T ;
Shi, YB ;
Evans, T .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (05) :2901-2911
[17]   INTESTINAL APOLIPOPROTEIN AI GENE-TRANSCRIPTION IS REGULATED BY MULTIPLE DISTINCT DNA ELEMENTS AND IS SYNERGISTICALLY ACTIVATED BY THE ORPHAN NUCLEAR RECEPTOR, HEPATOCYTE NUCLEAR FACTOR-4 [J].
GINSBURG, GS ;
OZER, J ;
KARATHANASIS, SK .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (01) :528-538
[18]  
HadzopoulouCladaras M, 1997, J BIOL CHEM, V272, P539
[19]   Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis [J].
Hayhurst, GP ;
Lee, YH ;
Lambert, G ;
Ward, JM ;
Gonzalez, FJ .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (04) :1393-1403
[20]  
JAMES R, 1994, J BIOL CHEM, V269, P15229