A Model for Initiation of Mosaic HOX Gene Expression Patterns by Non-Coding RNAs in Early Embryos

There is growing appreciation for the role of non-coding (nc) RNA in regulation of HOX genes of Drosophila. Our data suggest that current models for activation by ncRNA at the bithorax complex (BX-C) genes are mistaken. We propose that bxd and iab ncRNAs repress coding HOX genes Ultrabithorax and abdominal A, respectively, by transcriptional interference. It is not clear how regulation by non-coding RNAs is integrated with other regulatory mechanisms at HOX loci. We suggest that non-coding RNAs regulated by the trithorax group of epigenetic regulators have an early transient role in repression of HOX genes at the bithorax complex. Later, we propose that repression by HOX proteins, and members of the Polycomb group take over from repression by ncRNAs. We discuss emerging research questions in light of this model.