The effect of DNA signals on nucleosome formation, chromatin structure, and chromosome function
Abstract
Much of the human genome is non-coding and it seems likely that at least some of the non-coding DNA is functionally important. However, only little is known about the possible function of the bulk of the human genome. Since essentially all the nuclear DNA is packaged into chromatin, it is likely that functional effects of non-coding DNA are mediated by the chromatin structure. By making use of human genomic sequence information now available, we showed that a specific set of periodic DNA motifs (period-10 VWG/CWB) encoded in genomic DNA is predicted to influence human chromosome function. The basic building block of chromatin is a nucleosome, composed of 147 bp of DNA wrapped ∼1.7 times around the histone core. It has been believed that the DNA motif of AA/AT/TA/TT and CC/CG/GC/GG at approximately every 10 base pair periods with the A/T-rich and G/C-rich motifs offset 5 base pairs bend DNA preferentially around the histone core of the nucleosome. Additionally, regularly oscillating period-10 VWG/CWB motif was implicated to mediate arrangement of chromatin, or the formation of regular nucleosome arrays. However, most of known DNA bending rules in nucleosome was derived in correlative ways. By using a series of designed sequences, we tested directly those DNA motifs on nucleosome formation by competitive nucleosome reconstitution assay. We found that periodic-10 bp TA di-nucleotides in some sequence contexts extremely prefer nucleosome formation by compressing the DNA minor groove. The direct measurement of nucleosome-forming ability for other periodic TA dinucleotide sequences showed the novel properties of TA di-nucleotide in nucleosome formation. We suggested how these data can be reconciled with previous findings. These experimental results should allow us to predict chromatin structure variations, and possible signatures of regulatory regions of large genome inherent in the DNA sequence.
Degree
Ph.D.
Advisors
Stein, Purdue University.
Subject Area
Biochemistry|Bioinformatics
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