Process And Analysis Methods For Nucleosome Data

In eukaryotic cells, nucleosomes is the basic unit of chromatins. The nucleosome position is dynamic for various cell types and biological states, for the purpose of releasing different DNA sequence fragments and exposing different transcription factor binding sites for the recognition and combination of transcription factors, which will lead to specific gene expression. Therefore, it is of great significance to analyze nucleosome signals. Currently, there are few methods for analyzing the nucleosome signals based on statistical hypothesis testing methods, however, none takes specific dynamic behaviour into consideration.We develop a nucleosome alignment method based on the dynamic programming algorithm, AlignNuP, which is capable to compare nucleosome positions from two cells, recognize the behaviors of nucleosomes moving or missing to analysis and predict the transcriptional regulation. Given peak lists standing for nucleosome positions, to align the peaks from two samples, our method accumulate all pair scores for match, replacement or deletion and choose the maximum one as the optimal alignment. On the basis of nucleosome alignment results, our method could find one-by-one correspondence between nucleosome positions in different cell stages, as well as the conservative stable and variable regions, which can be further used to recognize dynamic behaviors of nucleosome shift and eviction.We applied AlignNuP to calculate nucleosome dynamic positions data between CD4+T activated and resting cells from human body. The results suggested that nucleosome deletion tends to happen in transcription start sites, when the CD4+T cell state changes. These deletion could even affect the phase of nucleosomes downstream to regulate the gene expression level. However, in intronless genes, nucleosome shift rather than deletion happened, which may result from these polyA sites in the upstream of transcription start sites. The results indicated that that nucleosome positioning partly depends on the DNA sequence in intronless genes.Our method was also applied to the analysis for yeast nucleosome data. The result showed that the nucleosomes were missing near RNA polymerase Ⅱ binding sites when the cell is aging, which reveals that histones compete with transcriptional machine for binding to DNA. In addition, after histone mutation, a large scale of nucleosomes changed their positions and the majority of nucleosome deletion happened in the 200bp upstream of transcription start sites, to induce gene expression.