The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy

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  • Additional Information
    • Publication Information:
      Public Library of Science
    • Publication Date:
      2009
    • Subject Terms:
    • Abstract:
      Introduction The subtelomeric regions that lie between the telomeres and the proximal gene-rich regions display a variable size distribution and contribute to genome evolution but also human disorders [1]. In [...]
      Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD), which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s) through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients.
    • ISSN:
      1553-7390
    • Rights:
      Copyright 2009 Gale, Cengage Learning. All rights reserved.
      COPYRIGHT 2009 Public Library of Science
    • Accession Number:
      edsgcl.195267857
  • Citations
    • ABNT:
      OTTAVIANI, A. et al. The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy. PLoS Genetics, [s. l.], n. 2, 2009. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857. Acesso em: 30 out. 2020.
    • AMA:
      Ottaviani A, Rival-Gervier S, Boussouar A, et al. The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy. PLoS Genetics. 2009;(2). Accessed October 30, 2020. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857
    • APA:
      Ottaviani, A., Rival-Gervier, S., Boussouar, A., Foerster, A. M., Rondier, D., Sacconi, S., Desnuelle, C., Gilson, E., & Magdinier, F. (2009). The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy. PLoS Genetics, 2.
    • Chicago/Turabian: Author-Date:
      Ottaviani, Alexandre, Sylvie Rival-Gervier, Amina Boussouar, Andrea M. Foerster, Delphine Rondier, Sabrina Sacconi, Claude Desnuelle, Eric Gilson, and Frederique Magdinier. 2009. “The D4Z4 Macrosatellite Repeat Acts as a CTCF and A-Type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy.” PLoS Genetics, no. 2. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857.
    • Harvard:
      Ottaviani, A. et al. (2009) ‘The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy’, PLoS Genetics, (2). Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857 (Accessed: 30 October 2020).
    • Harvard: Australian:
      Ottaviani, A, Rival-Gervier, S, Boussouar, A, Foerster, AM, Rondier, D, Sacconi, S, Desnuelle, C, Gilson, E & Magdinier, F 2009, ‘The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy’, PLoS Genetics, no. 2, viewed 30 October 2020, .
    • MLA:
      Ottaviani, Alexandre, et al. “The D4Z4 Macrosatellite Repeat Acts as a CTCF and A-Type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy.” PLoS Genetics, no. 2, 2009. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857.
    • Chicago/Turabian: Humanities:
      Ottaviani, Alexandre, Sylvie Rival-Gervier, Amina Boussouar, Andrea M. Foerster, Delphine Rondier, Sabrina Sacconi, Claude Desnuelle, Eric Gilson, and Frederique Magdinier. “The D4Z4 Macrosatellite Repeat Acts as a CTCF and A-Type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy.” PLoS Genetics, no. 2 (2009). http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857.
    • Vancouver/ICMJE:
      Ottaviani A, Rival-Gervier S, Boussouar A, Foerster AM, Rondier D, Sacconi S, et al. The D4Z4 macrosatellite repeat acts as a CTCF and A-type Lamins-Dependent Insulator in Facio-Scapulo-Humeral Dystrophy. PLoS Genetics [Internet]. 2009 [cited 2020 Oct 30];(2). Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edsghw&AN=edsgcl.195267857