Rhox: A New Homeobox Gene Cluster

Abstract

Homeobox genes encode transcription factors notable for their ability to regulate embryogenesis. Here, we report the discovery of a cluster of 12 related homeobox genes on the X chromosome expressed in male and female reproductive tissues in adult mice. These reproductive homeobox on the X chromosome (Rhox) genes are expressed in a cell type-specific manner; several are hormonally regulated, and their expression pattern during postnatal testis development corresponds to their chromosomal position. Most of the Rhox genes are expressed in Sertoli cells, the nurse cells in direct contact with developing male germ cells, suggesting that they regulate the expression of somatic-cell gene products critical for germ cell development. In support of this, targeted disruption of Rhox5 increased male germ cell apoptosis and reduced sperm production, sperm motility, and fertility. Identification of this family of homeobox genes provides an opportunity to study colinear gene regulation and the transcriptional control of reproduction.

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

“…The Rhox homeobox genes are selectively expressed in male and female reproductive tissues, and thus they are likely to encode a set of transcription factors devoted to promoting and regulating gametogenesis (44). In support of this, we recently showed that mutational inactivation of Rhox5 causes aberrant germ cell apoptosis in stages V to XI of the seminiferous epithelial cycle, increased germ-cell apoptosis in stages I to IV and XII of the cycle, decreased sperm cell count, impaired sperm motility, and subfertility in mice (39). These aberrations are not the result of a germ cell defect but, rather, a Sertoli cell defect, as the Rhox5 gene and RHOX5 protein are expressed specifically in Sertoli cells within the postnatal and adult testis (38,51,59).…”

“…1B, WT). Cells incubated without R1881 and the AR expression plasmid expressed only low levels of luciferase from the Pp reporter vector (only slightly above that of pRL-null), consistent with earlier studies showing that the Pp depends on AR and androgen for expression (3,39,51). To assess whether AR might directly regulate the Pp, we scanned the 0.6-kb Pp 5Ј flanking region for sequences conforming to consensus ARbinding sites (androgen-response elements, or AREs) (57).…”

“…Real-time RT-PCR analysis of enriched Sertoli cells (39) showed that only Gata2 mRNA was significantly expressed (data not shown). Gata2 transcripts were present in both the Sertoli and interstitial cell fractions, even when they were subjected to hypotonic shock to remove residual germ cells (see Fig.…”

“…Rhox5 is the founding member of the reproductive homeobox on the X chromosome (Rhox) gene cluster that we recently identified (24,39,58). The Rhox gene cluster resides on the X chromosome and contains more than 30 genes in mice, making it the largest homeobox gene cluster known in any species (29,40,44,65).…”

shRNA Mediated RHOXF1 Silencing Influences Expression of BCL2 but not CASP8 in MCF-7 and MDA-MB-231 Cell Lines

“…They have been shown to be expressed in both germ cells and somatic cells of reproductive tract (MacLean and Wilkinson, 2010). As most of Rhox genes are expressed on Sertoli cells which are known as "nurse" sells of the testis and have close interaction with developing germ cells, it has been deduced that Rhox genes products can regulate the expression of somatic cell gene products vital for germ cell development (Maclean et al, 2005). In addition, targeted Rhox5 knock out has resulted in increased male germ cell apoptosis and consequently reduced sperm count and fertility (Maclean et al, 2005).…”