genomic sequence is highly predictive of local nucleosome depletion基因组序列高度预测当地的核小体损耗.pdfVIP

Genomic Sequence Is Highly Predictive of Local Nucleosome Depletion Guo-Cheng Yuan1,2,*, Jun S. Liu1,3,* 1 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America, 3 Department of Statistics, Harvard University, Cambridge, Massachusetts, United States of America The regulation of DNA accessibility through nucleosome positioning is important for transcription control. Computational models have been developed to predict genome-wide nucleosome positions from DNA sequences, but these models consider only nucleosome sequences, which may have limited their power. We developed a statistical multi-resolution approach to identify a sequence signature, called the N-score, that distinguishes nucleosome binding DNA from non-nucleosome DNA. This new approach has significantly improved the prediction accuracy. The sequence information is highly predictive for local nucleosome enrichment or depletion, whereas predictions of the exact positions are only modestly more accurate than a null model, suggesting the importance of other regulatory factors in fine-tuning the nucleosome positions. The N-score in promoter regions is negatively correlated with gene expression levels. Regulatory elements are enriched in low N-score regions. While our model is derived from yeast data, the N- score pattern computed from this model agrees well with recent high-resolution protein-binding data in human. Citation: Yuan G-C, Liu JS (2008) Genomic sequence is highly predictive of local nucleosome depletion. PLoS Comput Biol 4(1): e13. doi:10.1371/journal.pcbi.0040013 Introduction positions also helps downstream functional analyses, such as