Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape.

Vertebrate Hox genes encode transcription factors operating during the development of multiple organs and structures. However, the evolutionary mechanism underlying this remarkable pleiotropy remains to be fully understood. Here, we show that Hoxd8 and Hoxd9, two genes of the HoxD complex, are transcribed during mammary bud (MB) development. However, unlike in other developmental contexts, their coexpression does not rely on the same regulatory mechanism. Hoxd8 is regulated by the combined activity of closely located sequences and the most distant telomeric gene desert. On the other hand, Hoxd9 is controlled by an enhancer-rich region that is also located within the telomeric gene desert but has no impact on Hoxd8 transcription, thus constituting an exception to the global regulatory logic systematically observed at this locus. The latter DNA region is also involved in Hoxd gene regulation in other contexts and strongly interacts with Hoxd9 in all tissues analyzed thus far, indicating that its regulatory activity was already operational before the appearance of mammary glands. Within this DNA region and neighboring a strong limb enhancer, we identified a short sequence conserved in therian mammals and capable of enhancer activity in the MBs. We propose that Hoxd gene regulation in embryonic MBs evolved by hijacking a preexisting regulatory landscape that was already at work before the emergence of mammals in structures such as the limbs or the intestinal tract.


How mammary glands appeared in the course of evolution

Elements of the regulatory networks controlling Hox gene expression were hijacked, enabling some of these genes to be reused to form mammary buds. This study, published during the week of November 14, 2016 in PNAS, was led by Leonardo Beccari, from the team of Denis Duboule.


Revisiting germ line de novo mutations

06.12.2016 16:15, A100 (Sciences II)

Michel Georges (University of Liege, Belgium).
hosted by: Michel Milinkovitch.


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