IMR Press / FBL / Volume 12 / Issue 12 / DOI: 10.2741/2422

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Chromatin structure of repeating CTG/CAG and CGG/CCG sequences in human disease
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1 Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA
Front. Biosci. (Landmark Ed) 2007, 12(12), 4731–4741; https://doi.org/10.2741/2422
Published: 1 May 2007
Abstract

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.

Keywords
Chromatin structure
Nucleosome assembly
Triplet expansion disease
Myotonic dystrophy
Fragile X syndrome
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