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The  Hox  clusters play a crucial role in body patterning during animal development. They encode both  Hox  transcription factor and micro-RNA genes that are activated in a precise temporal and spatial sequence that follows their chromosomal order. These remarkable collinear properties confer functional unit status for  Hox  clusters. We developed the TranscriptView platform to establish high resolution transcriptional profiling and report here that transcription in the  Hox  clusters is far more complex than previously described in both human and mouse. Unannotated transcripts can represent up to 60% of the total transcriptional output of a cluster. In particular, we identified 14 non-coding Transcriptional Units antisense to  Hox  genes, 10 of which (70%) have a detectable mouse homolog. Most of these Transcriptional Units in both human and mouse present conserved sizeable sequences (>40 bp) overlapping  Hox  transcripts, suggesting that these  Hox  antisense transcripts are functional.  Hox  clusters also display at least seven polycistronic clusters, i.e., different genes being co-transcribed on long isoforms (up to 30 kb). This work provides a reevaluated framework for understanding  Hox  gene function and dys-function. Such extensive transcriptions may provide a structural explanation for  Hox  clustering.

Extensive Polycistronism and Antisense Transcription in the Mammalian Hox Clusters