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BMC Genomics

, 14:310



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

AbbreviationsHMEHistone-modification enzyme

FAIREFormaldehyde-assisted isolation of regulatory elements

DCSRDifferential chromatin-state region

NDCSRNon-differential chromatin-state region

CMDChromatin motif database

SNPSingle nucleotide polymorphism

TFTranscription factor

TFeTranscription factor encyclopedia

hPDIhuman Protein-DNA Interactome

FPKMFragments Per Kilobase of transcript per Million mapped reads.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-14-310 contains supplementary material, which is available to authorized users.

Chia-Chun Yang, Michael J Buck contributed equally to this work.

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Autor: Chia-Chun Yang - Michael J Buck - Min-Hsuan Chen - Yun-Fan Chen - Hsin-Chi Lan - Jeremy JW Chen - Chao Cheng - Chun-Chi 


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