A 77-base pair LINE-like sequence elicits androgen-dependent mvdp/akr1-b7 expression in mouse vas deferens, but is dispensable for adrenal expression in rats.
Mvdp/akr1-b7 (mouse vas deferens protein/aldo-keto reductase 1-B7) encodes an enzyme responsible for detoxification of a steroidogenesis byproduct. MVDP/AKR1-B7 is expressed in both rat and mouse adrenal cortex under ACTH control, whereas strong androgen-dependent accumulation in the vas deferens is mouse specific. Comparison of the regulatory regions of the two orthologs reveals a strong identity, disrupted by acquisition of a 77-bp LINE-derived sequence in the mouse promoter. Although ACTH responsiveness is observed in both species, the absence of this 77-bp sequence in the rat is associated with changes in transcription initiation sites. Transfection studies demonstrate that the CCAAT/enhancer-binding protein and selective promoter factor 1-binding sites previously shown to be essential for cAMP/ACTH induction in the mouse are consequently dispensable in the rat. Our data support the idea that the most striking change generated by this acquisition is the strong, androgen-dependent, vas deferens expression observed in mouse. 1) In rat vas deferens, rakr1-b7 expression is barely detectable and is not androgen sensitive. 2) Androgen receptor binds efficiently to an androgen response element within the 77-bp mouse-specific element. 3) Its insertion confers androgen sensitiveness to rakr1-b7 regulatory regions in an androgen response element-dependent manner in transient transfections. We propose that this acquired androgen-responsive region may be responsible for vas deferens androgen-regulated gene expression in vivo.
Unité Mixte de Recherche Centre National de la Recherche Scientifique, 6547 Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal Clermont II, Complexe Universitaire des Cézeaux, 63177 Aubiere, France.
Pierre
P
Val
Antoine
A
Martinez
Isabelle
I
Sahut-Barnola
Claude
C
Jean
Georges
G
Veyssière
Anne-Marie
AM
Lefrançois-Martinez
D000311:Adrenal Glands / Q000378:metabolism*; D000449:Aldehyde Reductase; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000187:drug effects*; D018398:Homeodomain Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D010053:Ovary / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013045:Species Specificity; D054339:Steroidogenic Factor 1; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014649:Vas Deferens / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1; D015383:Zona Fasciculata / Q000378:metabolism
D000728:Androgens; D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D051839:NFI Transcription Factors; D011506:Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D016329:Sp1 Transcription Factor; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C486169:Ybx1 protein, rat; D004247:DNA; C066498:Akr1b7 protein, mouse; D000449:Aldehyde Reductase