Pituitary homeobox 2 regulates adrenal4 binding protein/steroidogenic factor-1 gene transcription in the pituitary gonadotrope through interaction with the intronic enhancer.
Ad4BP/SF-1 [adrenal4 binding protein/steroidogenic factor-1 (NR5A1)] is a factor important for animal reproduction and endocrine regulation, and its expression is tightly regulated in the gonad, adrenal gland, ventromedial hypothalamic nucleus, and pituitary gonadotrope. Despite its functional significance in the pituitary, the mechanisms underlying pituitary-specific expression of the gene remain to be uncovered. In this study, we demonstrate by transgenic mouse assays that the pituitary gonadotrope-specific enhancer is localized within the sixth intron of the gene. Functionally, the enhancer recapitulates endogenous Ad4BP/SF-1 expression in the fetal Rathke's pouch to the adult pituitary gonadotrope. Structurally, the enhancer consists of several elements conserved among animal species. Mutational analyses confirmed the significance of these elements for the enhancer function. One of these elements was able to interact both in vitro and in vivo with Pitx2 (pituitary homeobox 2), demonstrating that pituitary homeobox 2 regulates Ad4BP/SF-1 gene transcription in the pituitary gonadotrope via interaction with the gonadotrope-specific enhancer.
Shima
Yuichi
Y
Division for Sex Differentiation, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Japan.
Zubair
Mohamad
M
Komatsu
Tomoko
T
Oka
Sanae
S
Yokoyama
Chikako
C
Tachibana
Taro
T
Hjalt
Tord A
TA
Drouin
Jacques
J
Morohashi
Ken-ichirou
K
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006062:Gonadotropins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D000097577:Homeobox Protein PITX2
D006062:Gonadotropins; D018398:Homeodomain Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2