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.
Val
Pierre
P
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.
Martinez
Antoine
A
Sahut-Barnola
Isabelle
I
Jean
Claude
C
Veyssière
Georges
G
Lefrançois-Martinez
Anne-Marie
AM
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