Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter

The sterol regulatory element binding-proteins (SREBPs) are transcription factors that regulate the genes of lipid metabolism. Cholesterol and unsaturated fatty acids regulate SREBPs. Giardia lamblia (GL) is an intestinal parasite and one of the earliest derived members within the eukaryotic lineage...

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Main Authors: Tilla S. Worgall, Sara R. Davis-Hayman, Marissa M. Magana, Peter M. Oelkers, Fernando Zapata, Rebecca A. Juliano, Timothy F. Osborne, Theodore E. Nash, Richard J. Deckelbaum
Format: Article
Language:English
Published: Elsevier 2004-05-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S002222752031840X
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author Tilla S. Worgall
Sara R. Davis-Hayman
Marissa M. Magana
Peter M. Oelkers
Fernando Zapata
Rebecca A. Juliano
Timothy F. Osborne
Theodore E. Nash
Richard J. Deckelbaum
spellingShingle Tilla S. Worgall
Sara R. Davis-Hayman
Marissa M. Magana
Peter M. Oelkers
Fernando Zapata
Rebecca A. Juliano
Timothy F. Osborne
Theodore E. Nash
Richard J. Deckelbaum
Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
Journal of Lipid Research
cyst-wall protein
encystations
sterol regulatory element binding protein
author_facet Tilla S. Worgall
Sara R. Davis-Hayman
Marissa M. Magana
Peter M. Oelkers
Fernando Zapata
Rebecca A. Juliano
Timothy F. Osborne
Theodore E. Nash
Richard J. Deckelbaum
author_sort Tilla S. Worgall
title Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
title_short Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
title_full Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
title_fullStr Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
title_full_unstemmed Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter
title_sort sterol and fatty acid regulatory pathways in a giardia lamblia-derived promoter
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2004-05-01
description The sterol regulatory element binding-proteins (SREBPs) are transcription factors that regulate the genes of lipid metabolism. Cholesterol and unsaturated fatty acids regulate SREBPs. Giardia lamblia (GL) is an intestinal parasite and one of the earliest derived members within the eukaryotic lineage. GLs exist as trophozoites and cysts. Growth in cholesterol depletion induces transcription of cyst-wall protein (CWP) genes that are upregulated during encystation. The hypothesis was investigated that SREBP-like pathways have a role in cwp gene transcription. Chinese hamster ovary cells were transfected with a cwp-2 promoter reporter construct. Incubation with cholesterol or oleate reduced cwp-2 mediated gene transcription to about half of the control. Incubation in sterol-depleted media, or in the presence of either an inhibitor of intracellular cholesterol movement or inhibitor of cholesterol synthesis, increased gene expression up to 3-fold. Overexpression of SREBPs increased reporter gene activity 2.5-fold. In the absence of functional SREBPs, cwp-2 was not regulated by cholesterol. Footprint analysis of cwp-2 reveals three novel binding sites for mammalian SREBPs with no homologies in other species or humans.The data show that SREBP binds to and can modulate transcription of a regulatory element from an ancient eukaryote and suggest the existence of an SREBP homolog in GL.
topic cyst-wall protein
encystations
sterol regulatory element binding protein
url http://www.sciencedirect.com/science/article/pii/S002222752031840X
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spelling doaj-931bacc434324af1bdfc383d99af1e562021-04-27T04:40:56ZengElsevierJournal of Lipid Research0022-22752004-05-01455981988Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoterTilla S. Worgall0Sara R. Davis-Hayman1Marissa M. Magana2Peter M. Oelkers3Fernando Zapata4Rebecca A. Juliano5Timothy F. Osborne6Theodore E. Nash7Richard J. Deckelbaum8Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104Department of Pathology, Columbia University, New York, NY 10032; Department of Pediatrics, Columbia University, New York, NY 10032; Institute of Human Nutrition, Columbia University, New York, NY 10032; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697; Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA 19104The sterol regulatory element binding-proteins (SREBPs) are transcription factors that regulate the genes of lipid metabolism. Cholesterol and unsaturated fatty acids regulate SREBPs. Giardia lamblia (GL) is an intestinal parasite and one of the earliest derived members within the eukaryotic lineage. GLs exist as trophozoites and cysts. Growth in cholesterol depletion induces transcription of cyst-wall protein (CWP) genes that are upregulated during encystation. The hypothesis was investigated that SREBP-like pathways have a role in cwp gene transcription. Chinese hamster ovary cells were transfected with a cwp-2 promoter reporter construct. Incubation with cholesterol or oleate reduced cwp-2 mediated gene transcription to about half of the control. Incubation in sterol-depleted media, or in the presence of either an inhibitor of intracellular cholesterol movement or inhibitor of cholesterol synthesis, increased gene expression up to 3-fold. Overexpression of SREBPs increased reporter gene activity 2.5-fold. In the absence of functional SREBPs, cwp-2 was not regulated by cholesterol. Footprint analysis of cwp-2 reveals three novel binding sites for mammalian SREBPs with no homologies in other species or humans.The data show that SREBP binds to and can modulate transcription of a regulatory element from an ancient eukaryote and suggest the existence of an SREBP homolog in GL.http://www.sciencedirect.com/science/article/pii/S002222752031840Xcyst-wall proteinencystationssterol regulatory element binding protein