The Male Hypermethylation (MHM) Region on the Chicken Z Chromosome: Female-Specific Transcription and its Biological Implication

Abstract

The human DM-related transcript 1 (DMRT1) and DMRT2 genes are located at the distal region of chromosome 9p24.3 and suggested to be involved in the differentiation of testis in a dosage dependent manner, because XY individuals hemizygous for these genes exhibit a high frequency of XY feminization (Raymond et al., 1999a). In mouse embryos, the expression of DMRT1 gene is first detected by RT-PCR at E9.5, the earliest stage of genital ridge formation, and its expression in genital ridges and in early gonads, as detected by RT-PCR and in situ hybridization, continues until E14.5 in both male and female embryos. At E15.5, its expression in the female declines significantly and becomes testis-specific in adults (Raymond et al., 1999b). In chickens, a single DMRT1 gene is located on the short arm of the Z chromosome, expressed in genital ridges of both male and female embryos at as early as stage 19 (~3-day) (Raymond et al., 1999b) but later its expression becomes male (testis)-specific as in mammals (this study; Figure 2A,B). In early chicken embryos at stages 25–31 (4.5- to 7-day), the level of DMRT1 mRNA is about 2-fold higher in males than in females (Raymond et al., 1999b and this study), which might have been attained by the absence of a mechanism to shut off the transcription on one of the Z chromosomes in males (Kuroda et al., 2001). It has been speculated that the apparently dosage-dependent expression of the DMRT1 gene in early chicken embryos may have a role in the sex determination (Raymond et al., 1999b). The exclusive expression of the DMRT1 gene in adult testis both in mammals and birds may also suggest that its gene expression is required for some essential functions in the differentiated testis.