EVOLUTIONARY CO-OPTION OF AN ANCESTRAL CLOACAL REGULATORY LANDSCAPE WITH THE EMERGENCE OF DIGITS AND GENITALS [ChIP-seq]
The existence of homologies between fins and tetrapod limb skeletal parts as well as of the nature of those mechanisms underlying the transition of the former towards the latter, have been a rich source of discussion for more than a century. While the recent use of gene expression patterns to try and infer evolutionary scenarios has been a popular and successful approach, in particular the distribution of Hox transcript domains, it has failed to provide clearcut evidence as to whether fishes do have bony elements related by ancestry to tetrapod hands and feet. In tetrapods, posterior Hoxd genes transcription in digits is controlled by a well-characterized series of enhancers forming a large regulatory landscape, which has its syntenic counterpart in zebrafish. We show here that the deletion of the orthologous landscape in fishes does not affect the transcription of these genes in fin buds. Instead, it abrogates hoxd expression in the cloaca, an essential structure related to the mammalian uro-genital sinus. We also report that Hoxd gene function in the mammalian uro-genital sinus depends on enhancers located in the same regulatory landscape and thus conclude that an ancestral Hox 'cloacal' regulation was co-opted, in tetrapod, as a playground to subsequently accompany the evolution of both external genitals and digits regulatory landscapes, along with the emergence of these developmentally and phylogenetically related structures. Overall design: Histone mark ChIP-seq experiments in wild type mouse urogenital sinuses. Please note that the CTCF ChIP-seq experiments in one mouse sample from GSE194418 and four zebrafish samples from GSE156096 have been re-analyzed: BioProject accession: PRJNA800459 GEO Sample      SRA Runs        BioSample       Title ==========      ========        =========       ===== GSM5835468   SRR17750150  SAMN25248179  ChIP_CTCF_E105_PT_rep1 BioProject accession: PRJNA656773 GEO Sample      SRA Runs        BioSample       Title ==========      ========        =========       ===== GSM4724551      SRR12435909     SAMN15802273    ChIP-seq in zebrafish wild-type embryos at 24hpf, replicate 1 GSM5344491      SRR14670351     SAMN19371946    ChIP-seq in zebrafish wild-type embryos at 24hpf, replicate 2 GSM5344494      SRR14670354     SAMN19371948    ChIP-seq in zebrafish wild-type embryos at 48hpf, replicate 1 GSM5344495      SRR14670355     SAMN19371947    ChIP-seq in zebrafish wild-type embryos at 48hpf, replicate 2 Please see more details in the 're-analysis_readme.txt'.