GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate the<i>Rhox5</i>Homeobox Gene in Sertoli Cells

Bhardwaj, Anjana; Rao, Manjeet K.; Kaur, Ramneet; Buttigieg, Miriam R.; Wilkinson, Miles

doi:10.1128/mcb.01170-07

Cited by 57 publications

(67 citation statements)

References 74 publications

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“…Androgen-dependent expression is conferred by the four AREs in region II (Barbulescu et al 2001, Geserick et al 2003, Bhardwaj et al 2008. These AREs also contribute to the tissue-and cell type-specific expression pattern of the Pp, as recently shown by Bhardwaj et al (2008).…”

Section: The Ppmentioning

confidence: 85%

“…This conclusion comes from several lines of evidence, including: i) Rhox5 mRNA levels (measured with either Rhox5 or Pp-specific probes) are dramatically reduced in animals deficient in the ability to produce LH (the peptide hormone responsible for inducing testosterone production in Leydig cells) as a result of hypophysectomy, chemical treatment, or genetic mutations , 1996c, Maiti et al 1996a, Sutton et al 1998; ii) testosterone reverses the defect in Rhox5 expression caused by loss of LH , Sutton et al 1998; and ix) the Pp possesses four androgen-response elements (AREs), each of which is required for its AR-and androgen-dependent expression in transfected cell lines (Barbulescu et al 2001, Geserick et al 2003, Bhardwaj et al 2008, Faus & Haendler 2008. Together, these studies strongly suggest that the Rhox5 Pp is a direct target of AR in Sertoli cells.…”

Section: The Ppmentioning

confidence: 99%

“…The highly androgen/AR-dependent expression of Rhox5 has lead to Rhox5 being widely used as a marker to examine perturbations disturbing androgen signaling (Sutton et al 1998, Barbulescu et al 2001, Geserick et al 2003, De Gendt et al 2004, MacLean & Wilkinson 2005, Terada et al 2005, Bhardwaj et al 2008, Prante et al 2008. Because the Rhox5 gene encodes a transcription factor, another implication of its androgen/AR-dependent expression is that it is a candidate to regulate the transcription of genes that mediate androgen action during spermatogenesis (MacLean & Wilkinson 2005).…”

Section: The Ppmentioning

confidence: 99%

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The Rhox genes

MacLean¹,

Wilkinson²

2010

Reproduction

110

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Homeobox genes encode transcription factors that have crucial roles in embryogenesis. A recently discovered set of homeobox genes -the Rhox genes -are expressed during both embryogenesis and in adult reproductive tissues. The 33 known mouse Rhox genes are clustered together in a single region on the X chromosome, while likely descendents of the primodial Rhox cluster, Arx and Esx1, have moved to other positions on the X chromosome. Here, we summarize what is known about the regulation and function of Rhox cluster and Rhox-related genes during embryogenesis and gametogenesis. The founding member of the Rhox gene cluster -Rhox5 (previously known as Pem) -has been studied in the most depth and thus is the focus of this review. We also discuss the unusually rapid evolution of the Rhox gene cluster.

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Section: The Ppmentioning

confidence: 85%

Section: The Ppmentioning

confidence: 99%

Section: The Ppmentioning

confidence: 99%

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The Rhox genes

MacLean¹,

Wilkinson²

2010

Reproduction

110

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“…This is supported by the observation that GATA4 downstream target genes involved in gonadal somatic cell function and steroidogenesis, including Mis or Star (Tremblay & Viger 1999, Hiroi et al 2004, were down-regulated in siGata4 induced mice. An additional plausible mechanism for disorders in spermatogenesis is a disturbed activation of the reproductive homeobox on the X chromosome gene by Gata4 deficiency in Sertoli cells (Bhardwaj et al 2008). In humans, data on disorders in the development or function of the male gonads have not been associated with GATA4 yet, but appear likely, since some mutations affect the activity of target gonadal promoters in vitro (Bouchard et al 2009).…”

Section: Reduction Of Gata4 Expression By 80% Does Not Impair the Funmentioning

confidence: 99%

Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

Thurisch

Liang²,

Sarioglu³

et al. 2009

Journal of Molecular Endocrinology

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Homozygous deficiency of the transcription factor Gata4 in mice causes lethality due to defects in ventral morphogenesis and heart tube formation. There is increasing evidence demonstrating that GATA4 function is also relevant for normal developed organ systems, including the heart and endocrinum. To analyze the implication of Gata4 beyond development, we generated transgenic mice expressing inducible small interfering RNA against Gata4. In longitudinal analysis, efficient suppression of Gata4 mRNA (down to 80% of wild-type levels) and protein expression in the heart was detected 38 days after induction of Gata4 short hairpin RNA. Decreased Gata4 expression was associated with reduction in the expression of known cardiac target genes, but the function of the heart remained unperturbed at 20-30% of normal Gata4 levels. Interestingly, Gata4 expression was almost abolished in the ovary and testis. This was accompanied in the testis by a significant reduction of GATA4 downstream target genes, such as the genes encoding Mullerian inhibiting substance (MIS) and steroidogenic acute regulatory (StAR) protein. By contrast, expression levels of Mis and Star were only slightly modified in the ovary, and concentrations of circulating FSH and LH were normal in female transgenic mice after induction of Gata4 short hairpin RNA. However, inhibition of Gata4 expression led to the formation of ovarian teratoma in 10% of females. Histology of the teratomas showed predominantly ectodermal and mesodermal structures. Our data demonstrate that Gata4 is critically involved in the function and integrity of the gonads in vivo.

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“…The Rhox5 gene depends on androgen and androgen receptor (AR) for expression in Sertoli cells Maiti et al 1996;Rao et al 2003;De Gendt et al 2004;Bhardwaj et al 2008). This suggests the possibility that RHOX5 is a transcription factor that mediates some of the actions of testosterone in spermatogenesis.…”

Section: Dna-binding Proteins That Regulate Spermatogenesismentioning

confidence: 99%

Transcription and post-transcriptional regulation of spermatogenesis

Bettegowda

Wilkinson

2010

Phil. Trans. R. Soc. B

Self Cite

134

101

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Spermatogenesis in mammals is achieved by multiple players that pursue a common goal of generating mature spermatozoa. The developmental processes acting on male germ cells that culminate in the production of the functional spermatozoa are regulated at both the transcription and posttranscriptional levels. This review addresses recent progress towards understanding such regulatory mechanisms and identifies future challenges to be addressed in this field. We focus on transcription factors, chromatin-associated factors and RNA-binding proteins necessary for spermatogenesis and/ or sperm maturation. Understanding the molecular mechanisms that govern spermatogenesis has enormous implications for new contraceptive approaches and treatments for infertility.

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

Cited by 57 publications

References 74 publications

The Rhox genes

The Rhox genes

Transgenic mice expressing small interfering RNA against Gata4 point to a crucial role of Gata4 in the heart and gonads

Transcription and post-transcriptional regulation of spermatogenesis

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