coTRaCTE predicts co-occurring transcription factors within cell-type specific enhancers

PLoS Computational Biology
Alena van BömmelMartin Vingron

Abstract

Cell-type specific gene expression is regulated by the combinatorial action of transcription factors (TFs). In this study, we predict transcription factor (TF) combinations that cooperatively bind in a cell-type specific manner. We first divide DNase hypersensitive sites into cell-type specifically open vs. ubiquitously open sites in 64 cell types to describe possible cell-type specific enhancers. Based on the pattern contrast between these two groups of sequences we develop "co-occurring TF predictor on Cell-Type specific Enhancers" (coTRaCTE) - a novel statistical method to determine regulatory TF co-occurrences. Contrasting the co-binding of TF pairs between cell-type specific and ubiquitously open chromatin guarantees the high cell-type specificity of the predictions. coTRaCTE predicts more than 2000 co-occurring TF pairs in 64 cell types. The large majority (70%) of these TF pairs is highly cell-type specific and overlaps in TF pair co-occurrence are highly consistent among related cell types. Furthermore, independently validated co-occurring and directly interacting TFs are significantly enriched in our predictions. Focusing on the regulatory network derived from the predicted co-occurring TF pairs in embryonic stem cells...Continue Reading

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Citations

May 20, 2020·Genome Research·Luca MarianiMartha L Bulyk
Jan 13, 2021·Disease Models & Mechanisms·Julia M T AuerDimitrios K Papadopoulos

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Methods Mentioned

BETA
ChIP-seq
ChIP-chip
two-hybrid
immunoprecipitation
ESR

Software Mentioned

ggplot2
ENCODE
Cytoscape
MASS package
Ensembl
TRANSFAC
BEDTools
circlize
TRAP
CoTRaCTE

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