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Pituitary Homeobox 2 Regulates Adrenal4 Binding Protein/Steroidogenic Factor-1 Gene Transcription in the Pituitary Gonadotrope through Interaction with the Intronic Enhancer

Shima, Yuichi; Zubair, Mohamad; Komatsu, Tomoko; Oka, Sanae; Yokoyama, Chikako; Tachibana, Taro; Hjalt, Tord LU ; Drouin, Jacques and Morohashi, Ken-Ichirou (2008) In Molecular Endocrinology 22(7). p.1633-1646
Abstract
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 (VMH), 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 6th 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... (More)
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 (VMH), 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 6th 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, demonstrating that Pitx2 regulates Ad4BP/SF-1 gene transcription in the pituitary gonadotrope via interaction with the gonadotrope-specific enhancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Endocrinology
volume
22
issue
7
pages
1633 - 1646
publisher
The Endocrine Society
external identifiers
  • wos:000257144500010
  • pmid:18417734
  • scopus:46349104886
ISSN
0888-8809
DOI
10.1210/me.2007-0444
language
English
LU publication?
yes
id
2e3b7195-56b9-40a9-bc11-e31bbd1d94bf (old id 1147309)
date added to LUP
2008-05-07 14:56:17
date last changed
2017-01-01 06:32:22
@article{2e3b7195-56b9-40a9-bc11-e31bbd1d94bf,
  abstract     = {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 (VMH), 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 6th 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, demonstrating that Pitx2 regulates Ad4BP/SF-1 gene transcription in the pituitary gonadotrope via interaction with the gonadotrope-specific enhancer.},
  author       = {Shima, Yuichi and Zubair, Mohamad and Komatsu, Tomoko and Oka, Sanae and Yokoyama, Chikako and Tachibana, Taro and Hjalt, Tord and Drouin, Jacques and Morohashi, Ken-Ichirou},
  issn         = {0888-8809},
  language     = {eng},
  number       = {7},
  pages        = {1633--1646},
  publisher    = {The Endocrine Society},
  series       = {Molecular Endocrinology},
  title        = {Pituitary Homeobox 2 Regulates Adrenal4 Binding Protein/Steroidogenic Factor-1 Gene Transcription in the Pituitary Gonadotrope through Interaction with the Intronic Enhancer},
  url          = {http://dx.doi.org/10.1210/me.2007-0444},
  volume       = {22},
  year         = {2008},
}