RT Journal Article
SR Electronic
T1 Probing transcription factor combinatorics in different promoter classes and in enhancers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 197418
DO 10.1101/197418
A1 Jimmy Vandel
A1 Océane Cassan
A1 Sophie Lèbre
A1 Charles-Henri Lecellier
A1 Laurent Bréhélin
YR 2018
UL http://biorxiv.org/content/early/2018/03/02/197418.abstract
AB In eukaryotic cells, transcription factors (TFs) are thought to act in a combinatorial way, by competing and collaborating to regulate common target genes. However, several questions remain regarding the conservation of these combina-tions among different gene classes, regulatory regions and cell types. We propose a new approach named TFcoop to infer the TF combinations involved in the binding of a tar-get TF in a particular cell type. TFcoop aims to predict the binding sites of the target TF upon the binding affinity of all identified cooperating TFs. The set of cooperating TFs and model parameters are learned from ChIP-seq data of the target TF. We used TFcoop to investigate the TF combina-tions involved in the binding of 106 TFs on 41 cell types and in four regulatory regions: promoters of mRNAs, lncRNAs and pri-miRNAs, and enhancers. We first assess that TFcoop is accurate and outperforms simple PWM methods for pre-dicting TF binding sites. Next, analysis of the learned models sheds light on important properties of TF combinations in different promoter classes and in enhancers. First, we show that combinations governing TF binding on enhancers are more cell-type specific than that governing binding in pro-moters. Second, for a given TF and cell type, we observe that TF combinations are different between promoters and en-hancers, but similar for promoters of mRNAs, lncRNAs and pri-miRNAs. Analysis of the TFs cooperating with the dif-ferent targets show over-representation of pioneer TFs and a clear preference for TFs with binding motif composition similar to that of the target. Lastly, our models accurately dis-tinguish promoters associated with specific biological processes.