Nucleosome assembly on CTG triplet repeats.
Expansion of CTG repeat sequences is associated with several human genetic diseases. We have examined the consequences of CTG repeat expansion for nucleosome assembly and positioning. Short CTG repeats are found within the most favored DNA sequences yet defined for nucleosome assembly. We find that as few as six CTG repeats will facilitate nucleosome assembly to a similar extent as the 50 or more repeats found in disease genes. Thus an increase in nucleosome stability on expansion of existing triplet repeats is unlikely to explain the acquisition of the disease phenotype. However, the CTG repeat sequence is efficiently wrapped around the histone octamer, preferring to associate with histones at the nucleosomal dyad. Thus short segments CTG repeat sequence will facilitate the assembly of a stable positioned nucleosome which might contribute to the expansion phenomenon and the functional organization of chromatin.
Godde
J S
JS
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2710, USA.
Wolffe
A P
AP
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D017931:DNA Primers; D030342:Genetic Diseases, Inborn / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011487:Protein Conformation; D013816:Thermodynamics; D018911:Trinucleotide Repeats; D014981:Xenopus
D017931:DNA Primers; D006657:Histones; D009707:Nucleosomes; D004247:DNA