Control of <i>Hoxd</i> gene transcription in the mammary bud by hijacking a preexisting regulatory landscape

Article Article scientifique Article Control of <i>Hoxd</i> gene transcription in the mammary bud by hijacking a preexisting regulatory landscape eng 2016 author Schep Ruben 707065 author Necsulea Anamaria 842885 author Rodriguez Carballo Edgardo 0000-0003-4321-508X 819920 author Guerreiro Isabel 744873 author Andrey Guillaume 0000-0002-0911-4907 555493 author Nguyen Huynh Thi Hanh 134563 author Marcet Virginie 529024 author Zakany Jozsef 29602 author Duboule Denis 28643 author Beccari Léonardo 777684 E7720-E7729 10.1073/pnas.1617141113 27856734 0027-8424 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. Animals Enhancer Elements Genetic Gene Expression Regulation Developmental Genes Homeobox Homeodomain Proteins/genetics/metabolism Mammary Glands Animal/embryology/growth & development/metabolism Mice Inbred C57BL Mice Inbred CBA Mice Transgenic Sequence Analysis RNA Transcription Genetic Dewey 590 44 Département de génétique et évolution 162 false 1268 Contrôle épigénétique du développement embryonnaire 999 818 Groupe Duboule Proceedings of the National Academy of Sciences 113 48 870bf097-42e3-46a1-a43a-75dcbdd339f0 Article (Published version) Public E7720.full.pdf 1555772 application/pdf openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution

Title	Published in	Year	Views	Downloads

Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape	Proceedings of the National Academy of Sciences	2016	409	404
HoxD gene regulation in the developing mammary bud		2015	161	15

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Schep, Ruben