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BMC Genomics

, 14:428

Human and rodent genomics


BackgroundChromatin plays a critical role in regulating transcription factors TFs binding to their canonical transcription factor binding sites TFBS. Recent studies in vertebrates show that many TFs preferentially bind to genomic regions that are well bound by nucleosomes in vitro. Co-occurring secondary motifs sometimes correlated with functional TFBS.

ResultsWe used a logistic regression to evaluate how well the propensity for nucleosome binding and co-occurrence of a secondary motif identify which canonical motifs are bound in vivo. We used ChIP-seq data for three transcription factors binding to their canonical motifs: c-Jun binding the AP-1 motif TGA-GTCA, GR glucocorticoid receptor binding the GR motif G-ACA-CGT-C, and Hoxa2 homeobox a2 binding the Pbx Pre-B-cell leukemia homeobox motif TGATTGAT. For all canonical TFBS in the mouse genome, we calculated intrinsic nucleosome occupancy scores INOS for its surrounding 150-bps DNA and examined the relationship with in vivo TF binding. In mouse mammary 3134 cells, c-Jun and GR proteins preferentially bound regions calculated to be well-bound by nucleosomes in vitro with the canonical AP-1 and GR motifs themselves contributing to the high INOS. Functional GR motifs are enriched for AP-1 motifs if they are within a nucleosome-sized 150-bps region. GR and Hoxa2 also bind motifs with low INOS, perhaps indicating a different mechanism of action.

ConclusionOur analysis quantified the contribution of INOS and co-occurring sequence to the identification of functional canonical motifs in the genome. This analysis revealed an inherent competition between some TFs and nucleosomes for binding canonical TFBS. GR and c-Jun cooperate if they are within 150-bps. Binding of Hoxa2 and a fraction of GR to motifs with low INOS values suggesting they are not in competition with nucleosomes and may function using different mechanisms.

KeywordsTFBS Nucleosome GR c-Jun AbbreviationsTFTranscription factor

TFBSTranscription factor binding site

GLMGeneralized linear model

INOSIntrinsic nucleosome occupancy score

DHSDNase I hypersensitive sites

PVEPercent of variance explained

PNOPPredicted nucleosome occupancy probability

GRGlucocorticoid receptor

Hoxa2Homeobox a2

PbxPre-B-cell leukemia homeobox

AUCArea under the ROC curve.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-14-428 contains supplementary material, which is available to authorized users.

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Autor: Ximiao He - Raghunath Chatterjee - Sam John - Hector Bravo - B K Sathyanarayana - Simon C Biddie - Peter C FitzGerald -


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