DiNuP: a systematic approach to identify regions of differential nucleosome positioning

Motivation: With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. Results: We describe a novel computational approach, DiNuP, that compares nucleosome profiles generated by high-throughput sequencing under various conditions. DiNuP provides a statistical P-value for each identified RDNP based on the difference of read distributions. DiNuP also empirically estimates the false discovery rate as a cutoff when two samples have different sequencing depths and differentiate reliable RDNPs from the background noise. Evaluation of DiNuP showed it to be both sensitive and specific for the detection of changes in nucleosome location, occupancy and fuzziness. RDNPs that were identified using publicly available datasets revealed that nucleosome positioning dynamics are closely related to the epigenetic regulation of transcription. Availability and implementation: DiNuP is implemented in Python and is freely available at http://www.tongji.edu.cn/~zhanglab/DiNuP. Contact: yzhang@tongji.edu.cn Supplementary Information: Supplementary data are available at Bioinformatics online.

[1]  K. Foster,et al.  FLO1 Is a Variable Green Beard Gene that Drives Biofilm-like Cooperation in Budding Yeast , 2008, Cell.

[2]  R. Kornberg,et al.  Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome , 1999, Cell.

[3]  Ting Wang,et al.  An improved map of conserved regulatory sites for Saccharomyces cerevisiae , 2006, BMC Bioinformatics.

[4]  K. Luger.  Dynamic nucleosomes , 2005, Chromosome Research.

[5]  Pamela A. Silver,et al.  Functional Specificity among Ribosomal Proteins Regulates Gene Expression , 2007, Cell.

[6]  Steven J. M. Jones,et al.  Dynamic Remodeling of Individual Nucleosomes Across a Eukaryotic Genome in Response to Transcriptional Perturbation , 2007, PLoS biology.

[7]  J. Workman,et al.  Alteration of nucleosome structure as a mechanism of transcriptional regulation. , 1998, Annual review of biochemistry.

[8]  Steven M. Johnson,et al.  Determinants of nucleosome organization in primary human cells , 2011, Nature.

[9]  Jun S. Song,et al.  Identifying Positioned Nucleosomes with Epigenetic Marks in Human from ChIP-Seq , 2008, BMC Genomics.

[10]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[11]  K. Struhl,et al.  Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo , 2009, Nature Structural &Molecular Biology.

[12]  Irene K. Moore,et al.  The DNA-encoded nucleosome organization of a eukaryotic genome , 2009, Nature.

[13]  Cizhong Jiang,et al.  Nucleosome positioning and gene regulation: advances through genomics , 2009, Nature Reviews Genetics.

[14]  Steven M. Johnson,et al.  A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. , 2008, Genome research.

[15]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[16]  Nathaniel D. Heintzman,et al.  Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome , 2007, Nature Genetics.

[17]  N. Friedman,et al.  Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae , 2005, PLoS biology.

[18]  Dustin E. Schones,et al.  Dynamic Regulation of Nucleosome Positioning in the Human Genome , 2008, Cell.

[19]  Kevin Struhl,et al.  Evidence for Eviction and Rapid Deposition of Histones upon Transcriptional Elongation by RNA Polymerase II , 2004, Molecular and Cellular Biology.

[20]  B. Franklin Pugh,et al.  High-Resolution Genome-wide Mapping of the Primary Structure of Chromatin , 2011, Cell.

[21]  Bryan J Venters,et al.  A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. , 2008, Genome research.

[22]  J. Mellor,et al.  Dynamic nucleosomes and gene transcription. , 2006, Trends in genetics : TIG.

[23]  Bing Li,et al.  The Role of Chromatin during Transcription , 2007, Cell.