Control of ACAT2 liver expression by HNF1
ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and h...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520329333 |
| _version_ | 1818601209953517568 |
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| author | Camilla Pramfalk Matthew A. Davis Mats Eriksson Lawrence L. Rudel Paolo Parini |
| author_facet | Camilla Pramfalk Matthew A. Davis Mats Eriksson Lawrence L. Rudel Paolo Parini |
| author_sort | Camilla Pramfalk |
| collection | DOAJ |
| description | ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of the HNF1 binding site in the DNA sequence abolished not only the basal promoter function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the transcription factors HNF1α and HNF1β interact with this region in the human ACAT2 gene in vitro and in vivo.These data indicate that a) the identified HNF1 binding site serves as a positive regulator sequence, b) the binding site is functionally active both in vivo and in vitro, and c) the transcription factors HNF1α and HNF1β, which bind to this site, play an important part in the regulation of the human ACAT2 promoter. |
| first_indexed | 2024-12-16T12:47:45Z |
| format | Article |
| id | doaj.art-b8ab7294fb6845ef93a3cff29c3a3ce3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T12:47:45Z |
| publishDate | 2005-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b8ab7294fb6845ef93a3cff29c3a3ce32022-12-21T22:31:15ZengElsevierJournal of Lipid Research0022-22752005-09-0146918681876Control of ACAT2 liver expression by HNF1Camilla Pramfalk0Matthew A. Davis1Mats Eriksson2Lawrence L. Rudel3Paolo Parini4Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital in Huddinge, S-141 86 Stockholm, SwedenDepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital in Huddinge, S-141 86 Stockholm, SwedenDepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157To whom correspondence should be addressed.; Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, NOVUM, Karolinska Institutet at Karolinska University Hospital in Huddinge, S-141 86 Stockholm, SwedenACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1 and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this report, we elucidate the mechanisms that control the liver-specific expression of the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an important liver-specific trans-acting element for the human ACAT2 gene using the human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of the HNF1 binding site in the DNA sequence abolished not only the basal promoter function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the transcription factors HNF1α and HNF1β interact with this region in the human ACAT2 gene in vitro and in vivo.These data indicate that a) the identified HNF1 binding site serves as a positive regulator sequence, b) the binding site is functionally active both in vivo and in vitro, and c) the transcription factors HNF1α and HNF1β, which bind to this site, play an important part in the regulation of the human ACAT2 promoter.http://www.sciencedirect.com/science/article/pii/S0022227520329333livercholesteroltranscription factorgene regulationmetabolismacyl-coenzyme A:cholesterol acyltransferase |
| spellingShingle | Camilla Pramfalk Matthew A. Davis Mats Eriksson Lawrence L. Rudel Paolo Parini Control of ACAT2 liver expression by HNF1 Journal of Lipid Research liver cholesterol transcription factor gene regulation metabolism acyl-coenzyme A:cholesterol acyltransferase |
| title | Control of ACAT2 liver expression by HNF1 |
| title_full | Control of ACAT2 liver expression by HNF1 |
| title_fullStr | Control of ACAT2 liver expression by HNF1 |
| title_full_unstemmed | Control of ACAT2 liver expression by HNF1 |
| title_short | Control of ACAT2 liver expression by HNF1 |
| title_sort | control of acat2 liver expression by hnf1 |
| topic | liver cholesterol transcription factor gene regulation metabolism acyl-coenzyme A:cholesterol acyltransferase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520329333 |
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