Wilms' Tumor Protein Wt1 Is an Activator of the Anti-Müllerian Hormone Receptor Gene <i>Amhr2</i>

Klattig, Jürgen; Sierig, Ralph; Kruspe, Dagmar; Besenbeck, Birgit; Englert, Christoph

doi:10.1128/mcb.01780-06

Cited by 61 publications

(52 citation statements)

References 62 publications

(61 reference statements)

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“…E, the Wt1(ϩKTS) isoform, which lacks 3 amino acids in its zinc finger domain (36), did not bind to the oligonucleotides (lanes 3, 6, and 9). ducts, are among the genes that are regulated by Wt1 (41,52,53). Consistently, male-to-female sex reversal or genital tract abnormalities were observed in XY patients with heterozygous Wt1 germ line mutations (54), underscoring the role of Wt1 in testis determination.…”

Section: Wt1 Regulates Adamts16 In Developing Kidneys and Gonadsmentioning

confidence: 66%

Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development

Jacobi¹,

Rudigier

Scholz

et al. 2013

Journal of Biological Chemistry

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Background: ADAMTS16 is a mammalian metalloproteinase with unknown function. Results: Transcription of the Adamts16 gene is regulated by Wilms tumor protein Wt1, and knockdown of Adamts16 reduces branching morphogenesis in cultured embryonic kidneys. Conclusion: Adamts16 is a Wt1 target gene during murine genitourinary development. Significance: The findings provide novel insights into gene regulatory networks controlling kidney and gonad development.

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Section: Wt1 Regulates Adamts16 In Developing Kidneys and Gonadsmentioning

confidence: 66%

Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development

Jacobi¹,

Rudigier

Scholz

et al. 2013

Journal of Biological Chemistry

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“…S8). Interestingly, we observed that amhr2, the receptor of amh (Wu et al 2010), and wt1a and wt1b, potential activators of amhr2 (Klattig et al 2007), also showed differential methylation between ZW/ZZ testes and ovaries (Supplemental Fig. S8).…”

Section: Genomic Methylation Patterns Are Consistent With Gonadal Difmentioning

confidence: 94%

Epigenetic modification and inheritance in sexual reversal of fish

Shao

Chen³

et al. 2014

Genome Res.

371

302

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Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, cooccurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.

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“…8B). Others have reported that the Amhr2 promoter is also regulated by NR5A1 and WT1 (Teixeira et al 1999, Hossain & Saunders 2003, Klattig et al 2007). Interestingly, we have shown these two factors synergize with GATA4 on multiple gonadal promoters including Sry, Cyp19a1, HSD3B2, and Inha (Tremblay & Viger 2001, Bouchard et al 2005, Martin et al 2005, Miyamoto et al 2008.…”

Section: Discussionmentioning

confidence: 99%

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

Bergeron¹,

Nadeau²,

Viger³

2015

Reproduction

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GATA4 is an essential transcription factor required for the initiation of genital ridge formation, for normal testicular and ovarian differentiation at the time of sex determination, and for male and female fertility in adulthood. In spite of its crucial roles, the genes and/or gene networks that are ultimately regulated by GATA4 in gonadal tissues remain to be fully understood. This is particularly true for the steroidogenic lineages such as Leydig cells of the testis where many in vitro (promoter) studies have provided good circumstantial evidence that GATA4 is a key regulator of Leydig cell gene expression and steroidogenesis, but formal proof is still lacking. We therefore performed a microarray screening analysis of MA-10 Leydig cells in which Gata4 expression was knocked down using an siRNA strategy. Analysis identified several GATA4-regulated pathways including cholesterol synthesis, cholesterol transport, and especially steroidogenesis. A decrease in GATA4 protein was associated with decreased expression of steroidogenic genes previously suspected to be GATA4 targets such as Cyp11a1 and Star. Gata4 knockdown also led to an important decrease in other novel steroidogenic targets including Srd5a1, Gsta3, Hsd3b1, and Hsd3b6, as well as genes known to participate in cholesterol metabolism such as Scarb1, Ldlr, Soat1, Scap, and Cyp51. Consistent with the decreased expression of these genes, a reduction in GATA4 protein compromised the ability of MA-10 cells to produce steroids both basally and under hormone stimulation. These data therefore provide strong evidence that GATA4 is an essential transcription factor that sits atop of the Leydig cell steroidogenic program.

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Wilms' Tumor Protein Wt1 Is an Activator of the Anti-Müllerian Hormone Receptor Gene Amhr2

Cited by 61 publications

References 62 publications

Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development

Transcriptional Regulation by the Wilms Tumor Protein, Wt1, Suggests a Role of the Metalloproteinase Adamts16 in Murine Genitourinary Development

Epigenetic modification and inheritance in sexual reversal of fish

GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway

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