title: A regulatory archipelago controls Hox genes transcription in digits.
abstract: The evolution of digits was an essential step in the success of tetrapods. Among the key players, Hoxd genes are coordinately regulated in developing digits, where they help organize growth and patterns. We identified the distal regulatory sites associated with these genes by probing the three-dimensional architecture of this regulatory unit in developing limbs. This approach, combined with in vivo deletions of distinct regulatory regions, revealed that the active part of the gene cluster contacts several enhancer-like sequences. These elements are dispersed throughout the nearby gene desert, and each contributes either quantitatively or qualitatively to Hox gene transcription in presumptive digits. We propose that this genetic system, which we call a "regulatory archipelago," provides an inherent flexibility that may partly underlie the diversity in number and morphology of digits across tetrapods, as well as their resilience to drastic variations.
authors: National Research Centre, Frontiers in Genetics, School of Life Sciences, Ecole Polytechnique Fédérale, Lausanne, Switzerland.
authors: Thomas
authors: T
authors: Montavon
authors: Natalia
authors: N
authors: Soshnikova
authors: Bénédicte
authors: B
authors: Mascrez
authors: Elisabeth
authors: E
authors: Joye
authors: Laurie
authors: L
authors: Thevenet
authors: Erik
authors: E
authors: Splinter
authors: Wouter
authors: W
authors: de Laat
authors: François
authors: F
authors: Spitz
authors: Denis
authors: D
authors: Duboule
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005121:Extremities / Q000196:embryology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014981:Xenopus
chemical_list: D018398:Homeodomain Proteins