High-Throughput Analysis of Promoter Occupancy Reveals New Targets for Arx, a Gene Mutated in Mental Retardation and Interneuronopathies
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central High-Throughput Analysis of Promoter Occupancy Reveals New Targets for Arx, a Gene Mutated in Mental Retardation and Interneuronopathies Marie-Lise Quille´ 1,2,3, Solenne Carat4., Sylvia Que´me´ner-Redon1,2,3., Edouard Hirchaud4, Daniel Baron4, Caroline Benech1,2,3,5, Jeanne Guihot1,2,3, Morgane Placet1,2,3, Olivier Mignen1,2,3, Claude Fe´rec1,2,3,5, Re´mi Houlgatte4, Gae¨lle Friocourt1,2,3* 1 Inserm U613, Brest, France, 2 Faculte´ de Me´decine et des Sciences de la Sante´, Brest University, Brest, France, 3 Laboratory of Molecular Genetics and Histocompatibility, Brest University Hospital, Brest, France, 4 Institut du Thorax, Inserm U915, Nantes University, Nantes, France, 5 Etablissement Franc¸ais du Sang (EFS) Bretagne, Brest, France Abstract Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox) gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets.
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