Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity

Publication date: 23 May 2017
Source:Cell Reports, Volume 19, Issue 8
Author(s): Songjoon Baek, Ido Goldstein, Gordon L. Hager
In response to activating signals, transcription factors (TFs) bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e., footprint). Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly because of a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility: footprinting and motif-flanking accessibility. The algorithm, termed bivariate genomic footprinting (BaGFoot), efficiently detects TF activity. BaGFoot is robust to different accessibility assays (DNase-seq, ATAC-seq), all examined peak-calling programs, and a variety of cut bias correction approaches. BaGFoot reliably predicts TF binding and provides valuable information regarding the TFs affecting chromatin accessibility in various biological systems and following various biological events, including in cases where an absolute footprint cannot be determined.

Graphical abstract

Teaser

Baek et al. describe a method to identify changes in transcription factor activity based on telltale signs they leave on chromatin. This approach reliably predicts the activity of various transcription factors from chromatin accessibility information. The method provides an unbiased way to isolate relevant factors without assays targeting specific factors.


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2qaPGLp
via IFTTT