Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes

Barbara Celegato, Daniele Capitanio, Mario Pescatori, Chiara Romualdi, Beniamina Pacchioni, Stefano Cagnin, Agnese Viganò, Luca Colantoni, Shajna Begum, Enzo Ricci, Robin Wait, Gerolamo Lanfranchi, Cecilia Gelfi

Research output: Contribution to journalArticle

Abstract

Here, we present the first study of a human neuromuscular disorder at transcriptional and proteomic level. Autosomal dominant facio-scapulo-humeral muscular dystrophy (FSHD) is caused by a deletion of an integral number of 3.3-kb KpnI repeats inside the telomeric region D4Z4 at the 4q35 locus. We combined a muscle-specific cDNA microarray platform with a proteomic investigation to analyse muscle biopsies of patients carrying a variable number of KpnI repeats. Unsupervised duster analysis divides patients into three classes, according to their KpnI repeat number. Expression data reveal a transition from fast-glycolytic to slow-oxidative phenotype in FSHD muscle, which is accompanied by a deficit of proteins involved in response to oxidative stress. Besides, FSHD individuals show a disruption in the MyoD-dependent gene network suggesting a coregulation at transcriptional level during myogenesis. We also discuss the hypothesis that D4Z4 contraction may affect in trans the expression of a set of genes involved in myogenesis, as well as in the regeneration pathway of satellite cells in adult tissue. Muscular wasting could result from the inability of satellite cells to successfully differentiate into mature fibres and from the accumulation of structural damages caused by a reactive oxygen species (ROS) imbalance induced by an increased oxidative metabolism in fibres.

Original languageEnglish
Pages (from-to)5303-5321
Number of pages19
JournalProteomics
Volume6
Issue number19
DOIs
Publication statusPublished - Oct 2006

Keywords

  • 2-D electrophoresis
  • FSHD
  • Gene expression profile
  • Human muscle
  • Mass spectrometry

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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    Celegato, B., Capitanio, D., Pescatori, M., Romualdi, C., Pacchioni, B., Cagnin, S., Viganò, A., Colantoni, L., Begum, S., Ricci, E., Wait, R., Lanfranchi, G., & Gelfi, C. (2006). Parallel protein and transcript profiles of FSHD patient muscles correlate to the D4Z4 arrangement and reveal a common impairment of slow to fast fibre differentiation and a general deregulation of MyoD-dependent genes. Proteomics, 6(19), 5303-5321. https://doi.org/10.1002/pmic.200600056