title: ZNF555 protein binds to transcriptional activator site of 4qA allele and ANT1: potential implication in Facioscapulohumeral dystrophy.
abstract: Facioscapulohumeral dystrophy (FSHD) is an epi/genetic satellite disease associated with at least two satellite sequences in 4q35: (i) D4Z4 macrosatellite and (ii) β-satellite repeats (BSR), a prevalent part of the 4qA allele. Most of the recent FSHD studies have been focused on a DUX4 transcript inside D4Z4 and its tandem contraction in FSHD patients. However, the D4Z4-contraction alone is not pathological, which would also require the 4qA allele. Since little is known about BSR, we investigated the 4qA BSR functional role in the transcriptional control of the FSHD region 4q35. We have shown that an individual BSR possesses enhancer activity leading to activation of the Adenine Nucleotide Translocator 1 gene (ANT1), a major FSHD candidate gene. We have identified ZNF555, a previously uncharacterized protein, as a putative transcriptional factor highly expressed in human primary myoblasts that interacts with the BSR enhancer site and impacts the ANT1 promoter activity in FSHD myoblasts. The discovery of the functional role of the 4qA allele and ZNF555 in the transcriptional control of ANT1 advances our understanding of FSHD pathogenesis and provides potential therapeutic targets.
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Kim
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Rich
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
authors.forename: Adam
authors.initials: A
authors.lastname: Karoutas
authors.affiliation: National Center for Biotechnology, Astana 010000, Kazakhstan.
authors.forename: Pavel
authors.identifier: http://orcid.org/0000-0003-2075-307X
authors.initials: P
authors.lastname: Tarlykov
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France Proteomic Platform, IRCIV Gustave Roussy, Villejuif 94408, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Cochet
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
authors.forename: Daria
authors.initials: D
authors.lastname: Malysheva
authors.affiliation: Thérapie des maladies du muscle strié, Institut de Myologie, UM76-Pierre et Marie CURIE University/U974-INSERM/UMR7215-CNRS, Paris 75013, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mamchaoui
authors.affiliation: Proteomic Platform, IRCIV Gustave Roussy, Villejuif 94408, France INSERM, CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
authors.forename: Vasily
authors.initials: V
authors.lastname: Ogryzko
authors.affiliation: CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France iryna.pirozhkova@gustaveroussy.fr.
authors.forename: Iryna
authors.initials: I
authors.lastname: Pirozhkova
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000096:biosynthesis / Q000235:genetics*; D000483:Alleles; D001665:Binding Sites; D002478:Cells, Cultured; D002894:Chromosomes, Human, Pair 4; D004276:DNA, Satellite; D004742:Enhancer Elements, Genetic; D056426:Genetic Loci; D006801:Humans; D008840:Microfilament Proteins; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics*; D032446:Myoblasts / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D033741:Adenine Nucleotide Translocator 1; D004276:DNA, Satellite; C101270:FRG1 protein, human; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C000604118:ZNF555 protein, human