title: Discovering chromatin motifs using FAIRE sequencing and the human diploid genome.
abstract: BACKGROUND
  Specific 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors: Institute of Molecular Biology, National Chung Hsing University, Taiwan, ROC.
authors: Chia-Chun
authors: CC
authors: Yang
authors: Michael J
authors: MJ
authors: Buck
authors: Min-Hsuan
authors: MH
authors: Chen
authors: Yun-Fan
authors: YF
authors: Chen
authors: Hsin-Chi
authors: HC
authors: Lan
authors: Jeremy J W
authors: JJ
authors: Chen
authors: Chao
authors: C
authors: Cheng
authors: Chun-Chi
authors: CC
authors: Liu
mesh_terms: D001483:Base Sequence; D002843:Chromatin / Q000235:genetics*; D030562:Databases, Protein; D004171:Diploidy; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D059372:Nucleotide Motifs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D014157:Transcription Factors
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