Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter: Evidence for SREBP as an ancient transcription factor

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)981-988
Number of pages8
JournalJournal of Lipid Research
Volume45
Issue number5
DOIs
StatePublished - May 1 2004

Fingerprint

Sterol Regulatory Element Binding Proteins
Giardia lamblia
Sterols
Transcription Factors
Fatty Acids
Transcription
Cholesterol
Genes
Anticholesteremic Agents
Cysts
Sterol Regulatory Element Binding Protein 2
Trophozoites
Oleic Acid
Cricetulus
Eukaryota
Unsaturated Fatty Acids
Reporter Genes
Lipid Metabolism
Gene expression
Ovary

Keywords

  • Cyst-wall protein
  • Encystations
  • Sterol regulatory element binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter : Evidence for SREBP as an ancient transcription factor. / Worgall, Tilla S.; Davis-Hayman, Sara R.; Magana, Marissa M.; Oelkers, Peter M.; Zapata, Fernando; Juliano, Rebecca A.; Osborne, Timothy F.; Nash, Theodore E.; Deckelbaum, Richard J.

In: Journal of Lipid Research, Vol. 45, No. 5, 01.05.2004, p. 981-988.

Research output: Contribution to journalArticle

Worgall, TS, Davis-Hayman, SR, Magana, MM, Oelkers, PM, Zapata, F, Juliano, RA, Osborne, TF, Nash, TE & Deckelbaum, RJ 2004, 'Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter: Evidence for SREBP as an ancient transcription factor', Journal of Lipid Research, vol. 45, no. 5, pp. 981-988. https://doi.org/10.1194/jlr.M400024-JLR200
Worgall, Tilla S. ; Davis-Hayman, Sara R. ; Magana, Marissa M. ; Oelkers, Peter M. ; Zapata, Fernando ; Juliano, Rebecca A. ; Osborne, Timothy F. ; Nash, Theodore E. ; Deckelbaum, Richard J. / Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter : Evidence for SREBP as an ancient transcription factor. In: Journal of Lipid Research. 2004 ; Vol. 45, No. 5. pp. 981-988.
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