The Role of D4Z4 in Facio-Scapulo-Humeral Dystrophy
Author Information
Author(s): Ottaviani Alexandre, Rival-Gervier Sylvie, Boussouar Amina, Foerster Andrea M., Rondier Delphine, Sacconi Sabrina, Desnuelle Claude, Gilson Eric, Magdinier Frédérique
Primary Institution: Laboratoire de Biologie Moléculaire de la Cellule, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique UMR 5239, Lyon, France
Hypothesis
Does the D4Z4 macrosatellite repeat function as an insulator in Facio-Scapulo-Humeral Dystrophy (FSHD)?
Conclusion
D4Z4 acts as a CTCF and A-type Lamins-dependent insulator, and its contraction contributes to the pathophysiology of FSHD.
Supporting Evidence
- D4Z4 acts as an insulator that protects transgenes from position effect.
- CTCF binding and insulation activity are lost upon multimerization of the repeats.
- FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats.
- Both CTCF and A-type Lamins are necessary for the anti-silencing function of D4Z4.
Takeaway
D4Z4 is a special DNA sequence that helps control gene activity, and when it gets shorter in some patients, it can lead to muscle problems.
Methodology
The study involved creating constructs with varying numbers of D4Z4 repeats integrated into the human genome to assess their effects on gene expression.
Limitations
The study primarily focuses on cellular models and may not fully represent in vivo conditions.
Participant Demographics
The study involved cells from FSHD patients and healthy individuals.
Statistical Information
P-Value
p<0.0001
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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