Abstract
ChIP-seq experiments detect the chromatin occupancy of known transcription factors in a genome-wide fashion. The comparisons of several species-specific ChIP-seq libraries done for different transcription factors have revealed a complex combinatorial and context-specific co-localization behavior for the identified binding regions. In this study we have investigated human derived ChIP-seq data to identify common cis-regulatory principles for the human transcription factor c-Fos. We found that in four different cell lines, c-Fos targeted proximal and distal genomic intervals show prevalences for either AP-1 motifs or CCAAT boxes as known binding motifs for the transcription factor NF-Y, and thereby act in a mutually exclusive manner. For proximal regions of co-localized c-Fos and NF-YB binding, we gathered evidence that a characteristic configuration of repeating CCAAT motifs may be responsible for attracting c-Fos, probably provided by a nearby AP-1 bound enhancer. Our results suggest a novel regulatory function of NF-Y in gene-proximal regions. Specific CCAAT dimer repeats bound by the transcription factor NF-Y define this novel cis-regulatory module. Based on this behavior we propose a new enhancer promoter interaction model based on AP-1 motif defined enhancers which interact with CCAAT-box characterized promoter regions.
Highlights
Transcription factors (TFs) are proteins that control gene expression through a variety of mechanisms such as enhancing the efficiency of the basal transcription complex to assemble or re-model chromatin
The analysis was done (a) by recording Receiver Operating Characteristic (ROC) curves with TRANSFAC matrices in order to identify the best classifier compared to non-overlapping cell-type specific DHS regions for each sequence set or (b) by applying the MEME program to identify de novo the most prevalent sequence motif in each ChIP-seq data set
We found that besides the activator protein 1 (AP-1) motif, which was expectedly indicative for some of the data sets, a couple of cell line specific ChIP-seq regions were characterized by position weight matrices (PWMs) for the transcription factor NF-Y, which binds to CCAAT boxes [21]
Summary
Transcription factors (TFs) are proteins that control gene expression through a variety of mechanisms such as enhancing the efficiency of the basal transcription complex to assemble or re-model chromatin. Each regulatory region is defined by an array of such TFBSs. The cooperative binding of multiple TFs to these closely located TFBSs determines the transcription activity of their target genes [1, 2]. The activity of a proximal or a distal region in a certain cellular context is associated with its epigenetic status such as DNA- or histone modification, and can be monitored by its sensitivity against DNase I attack [3, 4]. It is unclear whether the binding of a TF is the prerequisite or the consequence
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