Effects of triplet repeat sequences on nucleosome positioning and gene expression in yeast minichromosomes.
Triplet repeat sequences that cause human hereditary diseases can form a variety of DNA conformations. Since DNA structures act as determinants of chromatin structure, chromatin may be involved in mechanisms of these diseases. To address this issue, we examined effects of triplet repeat sequences on chromatin structure and gene expression in Saccharomyces cerevisiae. We show here that (1) (CTG)12 promotes nucleosome formation, (2) (CGG)12 disrupts an array of positioned nucleosomes, and (3) (GAA)12 has little effect on nucleosome formation. Also, we show that insertion of (CGG)12 increases gene expression of a UAS-less promoter about 10-fold, while (CTG)12 and (GAA)12 have no effect. Thus, expansion of triplet repeat sequences may cause improper expression of disease related genes, through their effects on chromatin structure.
Tomita
Nobuyuki
N
Department of Chemistry, Meisei University, Hino, Tokyo 191-8506, Japan.
Fujita
Ryo
R
Kurihara
Daichi
D
Shindo
Heisaburo
H
Wells
Robert D
RD
Shimizu
Mitsuhiro
M
D015825:Chromosomes, Fungal; D015870:Gene Expression; D009707:Nucleosomes; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D018911:Trinucleotide Repeats
D009707:Nucleosomes