In eukaryotic cells,
chromatin structure organizes genomic
DNA in a dynamic fashion, and results in regulation of many
DNA metabolic processes. The CTG/CAG and CGG/CCG repeating sequences involved in several neuromuscular degenerative diseases display differential abilities for the binding of
histone octamers. The effect of the repeating
DNA on
nucleosome assembly could be amplified as the number of repeats increases. Also, CpG methylation, and sequence interruptions within the triplet repeats exert an impact on the formation of
nucleosomes along these repeating DNAs. The two most common triplet expansion human diseases,
myotonic dystrophy 1 and
fragile X syndrome, are caused by the expanded CTG/CAG and CGG/CCG repeats, respectively. In addition to the expanded repeats and CpG methylation, histone modifications, chromatin remodeling factors, and
noncoding RNA have been shown to coordinate the
chromatin structure at both
myotonic dystrophy 1 and fragile X loci. Alterations in
chromatin structure at these two loci can affect transcription of these disease-causing genes, leading to disease symptoms. These observations have brought a new appreciation that a full understanding of disease gene expression requires a knowledge of the structure of the
chromatin domain within which the gene resides.