Motivation:Chromatin immuno-precipitation sequencing (ChIP-Seq) of histone post-translational modificationscoupled with de novo motif elucidation and enrichment analyses can identify transcription factors responsible fororchestrating transitions between cell-and disease-states. However,the identifiedregulatory elements can span several kilobases(kb)in length, whichcomplicatesmotif-based analyses.Restricting the lengthof thetarget DNAsequence(s)can reduce false positives. Therefore, we present HisTrader, a computational tool to identify the regions accessible to transcription factors, nucleosome free regions (NFRs), within histonemodification peaks to reduce the DNA sequence length required for motif analyses.

Results: HisTrader accurately identifies NFRs from H3K27Ac ChIP-seq profiles of the lung cancer cell line A549,which are validated by the presence of DNaseI hypersensitivity. In addition, HisTrader reveals that multiple NFRs are common within individualregulatory elements; an easily overlooked feature that should be considered to improve sensitivity of motif analysesusing histone modification ChIP-seq data