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Role of a Sterol Response Element in Thyroid Hormone Stimulation of Transcription of the Hepatic HMG‐CoA Reductase Gene in vivo
Author(s) -
Jackson Lindsey,
Lagor William R.,
Heller Richard,
Ness Gene
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a239-b
Subject(s) - stimulation , in vivo , transcription (linguistics) , electroporation , endocrinology , medicine , luciferase , reductase , promoter , response element , sterol regulatory element binding protein , biology , thyroid , hormone , chemistry , gene expression , gene , sterol , transfection , cholesterol , enzyme , biochemistry , genetics , linguistics , philosophy
In this study, in vivo electroporation was performed to introduce 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGR) promoter constructs into livers of hypothyroid (hypophysectomized) Sprague‐Dawley rats treated ± thyroid hormone (T 3 ) in an effort to define the elements required for T 3 ‐mediated stimulation of hepatic HMGR transcription. With both the −325 to +70 and −770 to +441 HMGR promoter‐luciferase constructs, administration of 0.25% thyroid powder resulted in significant 2‐fold stimulations of luciferase activity. Since it has been reported that T 3 acts to increase expression of hepatic sterol response element binding protein‐2 (SREBP‐2) in mice, we investigated the possibility that the sterol response element (SRE) at −165 to −158 in the rat HMGR promoter might be required for T 3 stimulation of transcription of this gene. The −325 to +70 HMGR construct was mutated between −165 and −158. In vivo electroporation of the mutant construct into livers of rats revealed that promoter activity was decreased and there was no response to T 3 . Thus, this proximal SRE appears to be involved in regulation by T 3 . Further examination of the rat HMGR promoter reveals an upstream SRE and TRE. Whether these elements also contribute to thyroid hormone stimulation of hepatic HMGR transcription in vivo remain to be investigated. (Supported in part by Grant 04‐TSP‐03 from the Florida Department of Health.)