Polycomb complex shapes the higher order of D4Z4 chromatin structure during differentiation of normal and FSHD muscle stem cells
Poster
Data di Pubblicazione:
2008
Citazione:
Polycomb complex shapes the higher order of D4Z4 chromatin structure during differentiation of normal and FSHD muscle stem cells / B. Bodega, S. Brunelli, F. Grasser, N. Locatelli, R. Meneveri, A. Marozzi, S. Mueller, E. Battaglioli, E. Ginelli. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 16:Sup.2(2008 May), pp. 32-33. ((Intervento presentato al convegno The European Human Genetics Conference tenutosi a Barcellona nel 2008.
Abstract:
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant
neuromuscolar disorder. FSHD involves a complex cascade of epigenetic
events following contraction of a D4Z4 repeat located on chromosome 4q35.2
(FSHD locus). Previous work has indicated that transgenic mice
overexpressing FRG1, a gene proximal to the deletion, showed a phenotype
resembling the FSHD disease. However, increased expression of FRG1 in
FSHD patients has not been a uniform finding and up to now, several studies
have failed in identifying the molecular mechanism affecting the FSHD locus
functionality.
We took advantage of ChIP/MeDIP and 3D immuno-FISH assays as
complementary approaches to depict the higher order of chromatin
organization of 4q35.2 region during myogenic differentiation of healthy and
FSHD myoblast and mesoangioblast stem cells. We found that FRG1
undergoes to muscle specific regulation through a two-step activation
mechanism, whereby removal of H3-K27 methylation and Polycomb complex
components precedes MyoD recruitment on the FRG1 promoter; intriguingly,
the same chromatin structure and PcG recruitment were contemporaneously
found on D4Z4 array, rendering the Polycomb complex the first molecular
player that link s FSHD locus to myogenic differentiation. Moreover, D4Z4 H3-
mK27 signals were strongly reduced in FSHD myoblasts in respect to controls,
suggesting the severe impairment of the PcG complex recruitment.
Nevertheless, molecular alterations of the D4Z4 array do not have in FSHD
myoblasts an effect in cis on FRG1 gene expression. These observations
evidence a role of 4q35 D4Z4 in muscle differentiation, probably through
inter-chromosomal interactions.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
B. Bodega, S. Brunelli, F. Grasser, N. Locatelli, R. Meneveri, A. Marozzi, S. Mueller, E. Battaglioli, E. Ginelli
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