Lysine Specific Demethylase 6A (KDM6A)

KDM6A is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. UTX is enriched around the transcription start sites of many HOX genes in primary human fibroblasts, in which HOX genes are differentially expressed, but is selectively excluded from the HOX loci in embryonic stem cells, in which HOX genes are largely silent. Consistently, RNA interference inhibition of UTX led to increased H3K27me3 levels at some HOX gene promoters. Importantly, morpholino oligonucleotide inhibition of a zebrafish UTX homolog resulted in misregulation of HOX genes and a striking posterior developmental defect, which was partially rescued by wildtype, but not by catalytically inactive, human UTX.