Dbx2 regulation in limbs suggests inter tad sharing of enhancers

Article Article scientifique Article Dbx2 regulation in limbs suggests inter tad sharing of enhancers eng 2021-03 2021-03 author Beccari Léonardo 0000-0001-6472-5105 Department of Genetics and Evolution University of Geneva Geneva Switzerland 777684 author Jaquier Gabriel Department of Genetics and Evolution University of Geneva Geneva Switzerland 777958 author Lopez‐Delisle Lucille School of Life Sciences Federal School of Technology (EPFL) Lausanne Switzerland author Rodriguez‐Carballo Eddie Department of Genetics and Evolution University of Geneva Geneva Switzerland author Mascrez Bénédicte Department of Genetics and Evolution University of Geneva Geneva Switzerland 644325 Département de génétique et évolution (Genev) (BIANI) author Gitto Sandra Department of Genetics and Evolution University of Geneva Geneva Switzerland 630910 Département de génétique et évolution (Genev) (BIANI) author Woltering Joost 0000-0002-2630-6572 Department of Genetics and Evolution University of Geneva Geneva Switzerland 668883 author Duboule Denis 0000-0001-9961-2960 Department of Genetics and Evolution University of Geneva Geneva Switzerland 28643 1280-1299 10.1002/dvdy.303 33497014 1058-8388 PMC8451760 https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/dvdy.303 Background During tetrapod limb development, the HOXA13 and HOXD13 transcription factors are critical for the emergence and organization of the autopod, the most distal aspect where digits will develop. Since previous work had suggested that the Dbx2 gene is a target of these factors, we set up to analyze in detail this potential regulatory interaction. Results We show that HOX13 proteins bind to mammalian‐specific sequences at the vicinity of the Dbx2 locus that have enhancer activity in developing digits. However, the functional inactivation of the DBX2 protein did not elicit any particular phenotype related to Hox genes inactivation in digits, suggesting either redundant or compensatory mechanisms. We report that the neighboring Nell2 and Ano6 genes are also expressed in distal limb buds and are in part controlled by the same Dbx2 enhancers despite being localized into two different topologically associating domains (TADs) flanking the Dbx2 locus. Conclusions We conclude that Hoxa13 and Hoxd genes cooperatively activate Dbx2 expression in developing digits through binding to mammalian specific regulatory sequences in the Dbx2 neighborhood. Furthermore, these enhancers can overcome TAD boundaries in either direction to co‐regulate a set of genes located in distinct chromatin domains. Hox TAD boundary Chromatin architecture Digit development Gene regulation Dewey 590 Dewey 570 European Research Council 588029 Swiss National Science Foundation Hox genes and the molecular bases of vertebrate development 138662 CH Projects 44 Département de génétique et évolution 162 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false Developmental dynamics 250 9 6593429b-aaf0-469a-b778-64242104fbc0 Article (Published version) Public DUBOULE03.pdf 16350488 application/pdf CC BY-NC-ND-4.0 bb595801775201d328fb8d42bff39dc375972e2dd100d6cc4f464e8c75201622 openAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

Title	Published in	Year	Views	Downloads

Dbx2 regulation in limbs suggests inter tad sharing of enhancers	Developmental dynamics	2021	113	62
Characterization of Dbx2 gene function and regulation in developing forelimbs		2018	100	5

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