Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations.

Details

Serval ID
serval:BIB_89C7CA117FEC
Type
Article: article from journal or magazin.
Collection
Publications
Title
Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations.
Journal
European journal of human genetics : EJHG
Author(s)
Tabolacci E., Moscato U., Zalfa F., Bagni C., Chiurazzi P., Neri G.
ISSN
1018-4813 (Print)
ISSN-L
1018-4813
Publication state
Published
Issued date
12/2008
Volume
16
Number
12
Pages
1487-1498
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Fragile X syndrome (FXS) is caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 gene and the subsequent methylation of all CpG sites in the promoter region. We recently identified, in unrelated FXS families, two rare males with an unmethylated full mutation, that is, with an expanded CGG repeat (>200 triplets) lacking the typical CpG methylation in the FMR1 promoter. These individuals are not mentally retarded and do not appear to be mosaic for premutation or methylated full mutation alleles. We established lymphoblastoid and fibroblast cell lines that showed essentially normal levels of the FMR1-mRNA but reduced translational efficiency of the corresponding mRNA. Epigenetic analysis of the FMR1 gene demonstrated the lack of DNA methylation and a methylation pattern of lysines 4 and 27 on histone H3 similar to that of normal controls, in accordance with normal transcription levels and consistent with a euchromatic configuration. On the other hand, histone H3/H4 acetylation and lysine 9 methylation on histone H3 were similar to those of typical FXS cell lines, suggesting that these epigenetic changes are not sufficient for FMR1 gene inactivation. These findings demonstrate remarkable consistency and suggest a common genetic mechanism causing this rare FMR1 epigenotype. The discovery of such a mechanism may be important in view of therapeutic attempts to convert methylated into unmethylated full mutations, restoring the expression of the FMR1 gene.

Keywords
Cell Line, Cells, Cultured, DNA Methylation/physiology, DNA Mutational Analysis, Epigenesis, Genetic/physiology, Euchromatin/chemistry, Euchromatin/physiology, Family, Female, Fibroblasts/metabolism, Fibroblasts/pathology, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/pathology, Humans, Male, Models, Biological, Mutation/physiology
Pubmed
Open Access
Yes
Create date
06/03/2017 17:23
Last modification date
20/08/2019 14:48
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