Abstract

I will present our recent data on the characterization of the regulatory landscape orchestrating the transcriptional initiation and early collinear expression of the clustered Hox genes, emblematic transcription factor-encoding genes that pattern the embryonic body. Upon mapping chromatin marks and tridimensional interactions in the megabases-long genomic region flanking the Hox clusters on their “early” side, we uncovered a number of regulatory elements potentially accounting for the priming and the early transcription of the Hox genes in the posterior primitive streak. We validated the importance of some of these enhancers of the HoxA cluster in transgenic reporter assays in vivo and after CRISPR Cas9-mediated deletion in Epiblast stem cells. The data suggest a scenario underlying the triggering of initial transcription and the sequential turning on of the clustered Hox genes in the early mouse embryo.

In the second part of the seminar I will address the issue of the downstream program of Hox and Cdx genes. These genes derived from the same Proto Hox ancestors and share a function in the generation and antero-posterior patterning of nascent embryonic tissues. Our previous data suggested that they are involved in maintaining the niche of progenitors for axial tissues. I will present our recent results on the identification of Cdx downstream targets likely mediating this activity.