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Nucleic Acids Res. 2015 Sep 30;43(17):8227-42. doi: 10.1093/nar/gkv721. Epub 2015 Jul 15.

ZNF555 protein binds to transcriptional activator site of 4qA allele and ANT1: potential implication in Facioscapulohumeral dystrophy.

Author information

1
CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
2
National Center for Biotechnology, Astana 010000, Kazakhstan.
3
CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France Proteomic Platform, IRCIV Gustave Roussy, Villejuif 94408, France.
4
Thérapie des maladies du muscle strié, Institut de Myologie, UM76-Pierre et Marie CURIE University/U974-INSERM/UMR7215-CNRS, Paris 75013, France.
5
Proteomic Platform, IRCIV Gustave Roussy, Villejuif 94408, France INSERM, CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France.
6
CNRS, University Paris-Sud, UMR-8126, Gustave Roussy, Villejuif 94408, France iryna.pirozhkova@gustaveroussy.fr.

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.

PMID:
26184877
PMCID:
PMC4787827
DOI:
10.1093/nar/gkv721
[Indexed for MEDLINE]
Free PMC Article

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