Discovering chromatin motifs using FAIRE sequencing and the human diploid genome

BMC Genomics

Methodology Article

Michael J Buck¹  Chao Cheng²  Yun-Fan Chen³  Min-Hsuan Chen³  Chun-Chi Liu⁴  Hsin-Chi Lan⁵  Jeremy JW Chen⁶  Chia-Chun Yang⁷ 

[1] Department of Biochemistry and the Center of Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY, USA;Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA;Institute for Quantitative Biomedical Sciences, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA;Institute of Genomics and Bioinformatics, National Chung Hsing University, Taiwan, ROC;Institute of Genomics and Bioinformatics, National Chung Hsing University, Taiwan, ROC;Institute of Biomedical Sciences, National Chung Hsing University, Taiwan, ROC;Agricultural Biotechnology Center, National Chung Hsing University, Taiwan, ROC;Institute of Molecular Biology, National Chung Hsing University, Taiwan, ROC;Institute of Molecular Biology, National Chung Hsing University, Taiwan, ROC;Institute of Biomedical Sciences, National Chung Hsing University, Taiwan, ROC;Agricultural Biotechnology Center, National Chung Hsing University, Taiwan, ROC;Institute of Molecular Biology, National Chung Hsing University, Taiwan, ROC;Institute of Genomics and Bioinformatics, National Chung Hsing University, Taiwan, ROC;

关键词: Read Depth;    Diploid Genome;    Chromatin Accessibility;    GM12878 Cell;    Heterozygous SNPs;   

DOI  :  10.1186/1471-2164-14-310

 received in 2012-05-24, accepted in 2013-04-30,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSpecific chromatin structures are associated with active or inactive gene transcription. The gene regulatory elements are intrinsically dynamic and alternate between inactive and active states through the recruitment of DNA binding proteins, such as chromatin-remodeling proteins.ResultsWe developed a unique genome-wide method to discover DNA motifs associated with chromatin accessibility using formaldehyde-assisted isolation of regulatory elements with high-throughput sequencing (FAIRE-seq). We aligned the FAIRE-seq reads to the GM12878 diploid genome and subsequently identified differential chromatin-state regions (DCSRs) using heterozygous SNPs. The DCSR pairs represent the locations of imbalances of chromatin accessibility between alleles and are ideal to reveal chromatin motifs that may directly modulate chromatin accessibility. In this study, we used DNA 6-10mer sequences to interrogate all DCSRs, and subsequently discovered conserved chromatin motifs with significant changes in the occurrence frequency. To investigate their likely roles in biology, we studied the annotated protein associated with each of the top ten chromatin motifs genome-wide, in the intergenic regions and in genes, respectively. As a result, we found that most of these annotated motifs are associated with chromatin remodeling, reflecting their significance in biology.ConclusionsOur method is the first one using fully phased diploid genome and FAIRE-seq to discover motifs associated with chromatin accessibility. Our results were collected to construct the first chromatin motif database (CMD), providing the potential DNA motifs recognized by chromatin-remodeling proteins and is freely available at http://syslab.nchu.edu.tw/chromatin.

【 授权许可】

Unknown   
© Yang et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.