The murine luteinizing hormone and follicle-stimulating hormone receptor genes: Transcription initiation sites, putative promoter sequences and promoter activity

Huhtaniemi, Ilpo; Eskola, Vesa; Pakarinen, Pirjo; Matikainen, Tiina; Sprengel, Rolf

doi:10.1016/0303-7207(92)90009-u

Cited by 81 publications

(40 citation statements)

References 24 publications

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“…Using several approaches, including transient transfection experiments and protein-DNA binding assays, several groups have dissected a large number of Sertoli cell promoters to address this question (16,21,28,43,54). While various difficulties have been encountered, including misexpression in inappropriate tissues or developmental stages (see introduction) or regulatory elements so prohibitively far from the promoter that they are not even present in a large ϳ400-kb bacterial artificial chromosome (23), there has been some progress.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence that this VOL. 28,2008 SERTOLI CELL-SPECIFIC GENE TRANSCRIPTION 2145 treatment successfully removed germ cells was the finding that the Sertoli cell-specific marker, Gata1, was increased in level by ϳ2.5-fold after hypotonic treatment of the Sertoli cell fraction, and the Leydig cell marker, leuteinizing hormone mRNA, was increased in level by ϳ4-fold after hypotonic treatment of the interstitial cell fraction (data not shown). Because the Gata2 mRNA signal was not increased in hypotonic-shocked Sertoli cells, this implied that it is also present in germ cells.…”

Section: Identification Of Ares Essential For Rhox5 Pp Transcriptionmentioning

confidence: 96%

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GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Bhardwaj

Rao

Kaur

et al. 2008

Molecular and Cellular Biology

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How Sertoli-specific expression is initiated is poorly understood. Here, we address this issue using the proximal promoter (Pp) from the Rhox5 homeobox gene. Its Sertoli cell-specific expression is achieved, in part, through a negative regulatory element that inhibits Pp transcription in non-Sertoli cell lines. Complementing this negative regulation is positive regulation conferred by four androgen-response elements (AREs) that interact with the androgen receptor (AR), a nuclear hormone receptor expressed at high levels in Sertoli cells. A third control mechanism is provided by a consensus GATA-binding site that is crucial for Pp transcription both in vitro and in vivo. Several lines of evidence suggested that GATA factors and AR act cooperatively to activate Pp transcription: (i) the GATA-binding site crucial for Pp transcription is in close proximity to two of the AREs, (ii) GATA and AR form a complex with the Pp in vitro, (iii) overexpression of GATA factors rescued expression from mutant Pp constructs harboring defective AREs, and (iv) incubation of a Sertoli cell line with testosterone triggered corecruitment of AR and GATA4 to the Pp. Collectively, our results suggest that the Rhox5 gene achieves Sertoli cell-specific transcription using a combinatorial strategy involving negative and cooperative positive regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Identification Of Ares Essential For Rhox5 Pp Transcriptionmentioning

confidence: 96%

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Bhardwaj

Rao

Kaur

et al. 2008

Molecular and Cellular Biology

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“…The structure of Fshr has been determined in a number of species, including rat (Heckert et al, 1992), mouse (Huhtaniemi et al, 1992;Tena-Sempere et al, 1999), human (Gromoll et al, 1994;Gromoll et al, 1996), sheep (Sairam and Subbarayan, 1997), tammar wallaby (Mattiske et al, 2002), and computationally predicted in the chimpanzee, bovine, dog, chicken and zebrafish (Table 1). In each, there are 10 exons, with exons 1-9 encoding the extracellular domain and exon 10 the transmembrane and intracellular domains (Fig.…”

Section: The Fshr Genementioning

confidence: 99%

“…Evaluation of this promoter region uncovered a number of important regulatory elements and transcription factors that establish basal promoter activity. For purposes of this review, discussion will primarily reflect data from our laboratory on rat Fshr, but notably, comparison to studies with mouse, sheep, and human 5′flanking regions revealed several key promoter features that are conserved between species (reviewed in Heckert, 2005;Huhtaniemi et al, 1992;Gromoll et al, 1994;Linder et al, 1994;Goetz et al, 1996;Sairam and Subbarayan, 1997;Heckert et al, 1998;Kim and Griswold, 2001). Transcription of rat Fshr initiates from two majors sites positioned 98bp and 80bp upstream of the translational start codon (Heckert et al, 1992).…”

Section: A the Fshr Promoter Regionmentioning

confidence: 99%

Transcriptional regulation of the FSH receptor: New perspectives

Hermann

Heckert

2007

Molecular and Cellular Endocrinology

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The cell-surface receptor for the gonadotropin follicle-stimulating hormone (FSH) is expressed exclusively on Sertoli cells of the testis and granulosa cells of the ovary. FSH signal transduction through its receptor (Fshr) is critical for the timing and maintenance of normal gametogenesis in the mammalian gonad. In the 13 years since the gene encoding Fshr was first cloned, the mechanisms controlling its transcription have been extensively examined, but a clear understanding of what drives its unique cell-specificity remains elusive. Current knowledge of basal Fshr transcription highlights the role of an E-box in the proximal promoter which is bound by the basic helix-loop-helix transcription factors upstream stimulatory factor 1 (Usf1) and Usf2. Recent studies utilizing knockout mice and chromatin immunoprecipitation validated the importance of Usf to Fshr transcription and demonstrated a sexually dimorphic requirement for the Usf proteins to maintain normal Fshr expression. Studies have also shown that the promoter region itself is insufficient for appropriate Fshr expression in transgenic mice, indicating Fshr transcription depends on regulatory elements that lie outside of the promoter. Identification of such elements has been propelled by recent availability of genome sequence data, which facilitated studies using comparative genomics, DNase I hypersensitivity mapping, and transgenic analysis with large fragments of DNA. This review will focus on the current understanding of transcriptional regulatory processes that control expression of rat Fshr, including recent advances from our laboratory.

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“…The transcriptional mechanisms regulating Fshr expression have been examined in a number of species, including human, mouse, rat, and sheep, with the majority of these studies utilizing transient transfection and protein-DNA binding experiments to identify regulatory elements within the promoter region (Huhtaniemi et al, 1992;Gromoll et al, 1994;Sairam and Subbarayan, 1997;Heckert et al, 1998;Heckert and Griswold, 2002). Importantly, these studies highlighted several conserved features of the Fshr promoter.…”

Section: Introductionmentioning

confidence: 99%

Distal regulatory elements are required for Fshr expression, in vivo

Hermann

Hornbaker

Maran

et al. 2007

Molecular and Cellular Endocrinology

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The gonadotropin follicle-stimulating hormone (FSH) is required for initiation and maintenance of normal gametogenesis and acts through a specific, cell-surface receptor (Fshr) present only on Sertoli and granulosa cells in the gonads. Despite extensive examination of the transcriptional mechanisms regulating Fshr, the sequences directing its expression to these cells remain unidentified. To establish the minimal region necessary for Fshr expression, we generated transgenic mice carrying a yeast artificial chromosome (YAC) that contained 413 kilobases (kb) of the rat Fshr locus (YAC60). Transgene expression, as determined by RT-PCR, was absent from immature testis and Sertoli cells, limited to germ cells of the adult testis, and never observed in the ovary. While the data is limited to only one transgenic line, it suggests that the 413kb region does not specify the normal spatiotemporal expression pattern of Fshr. Comparative genomics was used to identify potential distal regulatory elements, revealing seven regions of high evolutionary conservation (≥80% identity over 100bp or more), six of which were absent from the transgene. Functional examination of the evolutionary conserved regions (ECRs) by transient transfection revealed that all of the ECRs had modest transcriptional activity in Sertoli or myoid cells with two, ECR4 and ECR5, showing differential effects in expressing and non-expressing cells. These data reveal that distal regulatory regions (outside the 413kb in YAC60) are required for appropriate temporal and spatial Fshr expression and implicate the identified ECRs in transcriptional regulation of Fshr.

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The murine luteinizing hormone and follicle-stimulating hormone receptor genes: Transcription initiation sites, putative promoter sequences and promoter activity

Cited by 81 publications

References 24 publications

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Transcriptional regulation of the FSH receptor: New perspectives

Distal regulatory elements are required for Fshr expression, in vivo

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