Epigenetic regulation of the RHOX homeobox gene cluster and its association with human male infertility

摘要: The X-linked RHOX cluster encodes a set of homeobox genes that are selectively expressed in the reproductive tract. Members regulate target important for spermatogenesis promote male fertility mice. Studies show demethylating agents strongly upregulate expression mouse Rhox genes, suggesting they regulated by DNA methylation. However, whether this extends to human methylation directly regulates gene transcription and how relates infertility unknown. To address these issues, we first defined promoter regions performed gain- loss-of-function experiments determine is Our results indicated necessary sufficient silence expression. associates with infertility, evaluated status sperm from large cohort patients. Linear regression analysis revealed strong association between hypermethylation three independent types semen abnormalities. Hypermethylation was restricted specifically cluster; did not observe it immediately adjacent on X chromosome. suggest under an epigenetic control mechanism aberrantly We propose serves as marker idiopathic candidate exert causal role infertility.