Disease relevance of Rhox5

• The Pem gene is expressed in undifferentiated embryonal stem (ES) and embryonal carcinoma (EC) cell lines [1].
• The constructs were driven by the tyrosine aminotransferase steroid-responsive region (TAT-GRE4x-Luc), the mouse mammary tumor virus promoter (MMTV-Luc) and the Pem homeobox gene proximal promoter respectively (Pem-Luc) [2].

High impact information on Rhox5

• In support of this, targeted disruption of Rhox5 increased male germ cell apoptosis and reduced sperm production, sperm motility, and fertility [3].
• Expression of the homeobox gene Pem, which is androgen-regulated in SC, was severely decreased [4].
• Gpbox is a paired-like homeobox gene that colocalizes with two other members of the family, PsxI and Pem, on the proximal portion of the mouse X chromosome [5].
• The remaining two (Rhox5/Pem and Xist) were mapped to the X chromosome and were predominantly expressed in female blastocysts [6].
• Comparison of gene expression in male and female mouse blastocysts revealed imprinting of the X-linked gene, Rhox5/Pem, at preimplantation stages [6].

Biological context of Rhox5

• This identified a homeobox containing protein encoded by a placenta and embryonic expression gene, referred to as Pem [7].
• Thus, our study has identified that menin interacts with Pem, and the high expression of these proteins in the testis suggests a role in spermatogenesis [7].
• In addition, Pem ARE-1, but not ARE-2 or the steroid response element, showed some flexibility with regard to spacing between half-sites [8].
• In the adult testis, this promoter fragment targeted the transgene expression specifically to Sertoli cells during stages IV-VIII of the seminiferous epithelial cycle, thereby mimicking the expression pattern of the endogenous Pem gene [9].
• Our results suggest that there are at least two regulatory regions in the Pem proximal promoter: one that directs androgen receptor-dependent expression specifically in Sertoli cells within the testis and another that confers stage-specific expression in neonates and adults by acting as a negative regulator [9].

Anatomical context of Rhox5

• Three genes with a pattern closely resembling that of Pem, a prototypical androgen-regulated gene expressed in Sertoli cells, were selected for confirmation by quantitative RT-PCR and additional analysis [10].
• In adult mice both Men1 and Pem yielded strong signals in testis, Sertoli cells and particularly in seminiferous tubules [7].
• The Pem homeobox transcription factor is expressed under androgen control in the testis and epididymis [8].
• When EBs were induced to differentiate, the outer cell layer of visceral or parietal endoderm expressed both Pem mRNA and protein [11].
• Although Pem transcripts are present in immortalized and tumorigenic cell lines from several different cell lineages, they are not detectable in any of 15 adult tissues tested [12].

Associations of Rhox5 with chemical compounds

• In the present study, we identified promoter sequences from the Pem homeobox gene that direct Sertoli cell-specific expression in an androgen-dependent and stage-specific manner [9].
• Injection of either testosterone or luteinizing hormone (LH) into hypophysectomized and hpg/hpg mice restored Pem expression in the testes to normal levels [13].
• The Pem recognition helix also has an isoleucine residue replacing an invariant asparagine residue and shares an asparagine residue at a third position with two other vertebrate homeoproteins, at least one of which binds to DNA only as a dimer [14].
• Pem mRNA is induced 35-fold in ES cells differentiated in the absence of retinoic acid [1].
• The interaction between mouse Pem and Cdc37 homolog was then confirmed by glutathione S-transferase pull-down assay, and the possible interaction model was suggested [15].

Other interactions of Rhox5

• Here, we show that the forced expression of Pem from the mouse Pgk-1 promoter in ES cells blocks the in vitro and in vivo differentiation of the cells [16].
• We have mapped the Pem gene to the proximal end of the mouse X chromosome, placing it within the Hprt region [17].
• EMSAs and mutational analysis of the Pem promoter allowed the identification of two functional androgen response elements named ARE-1 and ARE-2 [8].
• RNase protection, in situ hybridization, and Northern blot analyses of wild-type and germ-cell-deficient mutant mice (W(V)/ W(V)) localized Pem transcripts to Sertoli cells of the testis [13].
• Pem mRNA is increased in EC cells differentiated towards parietal or visceral endoderm, consistent with the abundant Pem expression in embryonic yolk sac [1].

Analytical, diagnostic and therapeutic context of Rhox5

• In this study, Pem gene expression was further examined using in situ hybridization and immunocytochemistry to determine the spatial distribution of Pem transcripts and protein in peri-implantation embryos and in embryoid bodies (EBs) [11].
• Sequence analysis of 12 species of mice and rats indicated that the Pem gene has evolved at a remarkably high rate [18].

References