Document Detail

Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD.
MedLine Citation:
PMID:  22522912     Owner:  NLM     Status:  MEDLINE    
The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. Twenty primary fibroblast (5 control, 10 FSHD1 and 5 FSHD2) and 26 primary myoblast (9 control, 12 FSHD1 and 5 FSHD2) cultures originating from patients with FSHD and controls were analyzed. Histone modification levels were determined by chromatin immunoprecipitation. We examined correlations between the chromatin compaction score (ChCS) defined by the H3K9me3:H3K4me2 ratio and an age corrected clinical severity score (CSS) or muscle pathology score (MPS). Possible relationships were investigated using linear regression analysis and significance was tested by Pearson's product-moment coefficient.   We found a significant difference of the ChCS between controls and patients with FSHD1 and between controls and patients with FSHD2. Tissue specific differences in ChCS were also observed. We also found a near-significant relationship between ChCS and the age corrected CSS in fibroblasts but not in myoblasts. Surprisingly, we found a strong correlation between the MPS of the vastus lateralis and the CSS. Our results confirm the D4Z4 chromatin relaxation previously shown to be associated with FSHD in a small number of samples. A possible relationship between clinical and epigenetic parameters could be established in patient fibroblasts, but not in myoblasts. The strong correlation between the MPS of the vastus lateralis and the CSS suggests that this muscle can be used to study for surrogate markers of overall disease severity.
Judit Balog; Peter E Thijssen; Jessica C de Greef; Bharati Shah; Baziel G M van Engelen; Kyoko Yokomori; Stephen J Tapscott; Rabi Tawil; Silvère M van der Maarel
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-01
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-11-09     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  579-84     Citation Subset:  IM    
Department of Human Genetics; Leiden University Medical Center; Leiden, The Netherlands.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Chromatin / chemistry,  metabolism*
Chromatin Immunoprecipitation
Epigenesis, Genetic*
Fibroblasts / metabolism
Histones / chemistry,  metabolism*
Homeodomain Proteins / genetics*,  metabolism
Muscular Dystrophy, Facioscapulohumeral / genetics*,  metabolism,  pathology
Myoblasts / metabolism
Promoter Regions, Genetic*
Protein Processing, Post-Translational
Regression Analysis
Severity of Illness Index
Grant Support
Reg. No./Substance:
0/Chromatin; 0/DUX4 protein, human; 0/Histones; 0/Homeodomain Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Silencing of Wnt5a during colon cancer metastasis involves histone modifications.
Next Document:  Prolonged rock climbing activity induces structural changes in cerebellum and parietal lobe.