Deoxyribonucleic acid-protein interactions and expression of the human testis-specific lactate dehydrogenase promoter: transcription factor Sp1 plays a major role.
The human testis-specific lactate dehydrogenase c gene (ldh-c) shows an exceptionally large window of expression throughout pre- and postmeiotic stages of the male germ cell lineage. In order to characterize the multiple stage-specific transcription factors necessary for ldh-c expression, we previously characterized the human ldh-c core promoter. Here, we used a combination of gel retardation assays and an in vitro transcription system derived from human tissues to better define the elements that govern ldh-c transcription. Three classes of transcriptional regulators were defined by these experiments. 1) The Sp1 transcription factor is a testis-"enriched" protein that is absent from most somatic tissues and that appears to play a major role in determining ldh-c expression in the testis. Highest levels of Sp1 during spermatogenesis correlate with maxima of ldh-c expression. 2) The testis-specific cAMP response element modulator (CREM) transcription factor binds a cAMP response element (CRE)-like sequence located at position -433. This transcriptional activator might contribute to postmeiotic transcription of ldh-c. 3) Factors present in tissues negative for ldh-c expression appear to bind both the CRE-like sequence and an adjacent hormone response element. The presence of this element could be involved in regulating ldh-c through the glucocorticoid/androgen pathways at the early stages of ldh-c expression.
Bonny
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Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Cooker
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LA
Goldberg
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D001483:Base Sequence; D051786:Cyclic AMP Response Element Modulator; D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000378:metabolism*; D014018:Tissue Distribution; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D051786:Cyclic AMP Response Element Modulator; D004247:DNA; D007770:L-Lactate Dehydrogenase