Transcription factor binding predicts histone modifications in human cell lines

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Abstract
Significance: The regulation of gene expression is fundamental to biology and is classically predicated on binding of transcription factor proteins to DNA. This view is challenged by large-scale studies correlating gene expression with posttranslational modifications of the histone proteins with which DNA is complexed in cells. Here, we show through a large-scale computational study that histone modifications can be predicted with remarkable accuracy from transcription factor-binding profiles, recapitulating known interactions between transcription factors and chromatin-modifying enzymes. Our results demonstrate that associations between gene expression and histone modifications do not necessarily imply a direct regulatory role for these modifications, but can be explained equally well as an indirect effect of interactions between transcription factors and chromatin-modifying enzymes.

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