Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Asymmetric Conservation within Pairs of Co-occurred Motifs Mediates Weak Direct Transcription Factor Binding in ChIP-seq Data

Version 1 : Received: 25 July 2020 / Approved: 26 July 2020 / Online: 26 July 2020 (16:38:08 CEST)
Version 2 : Received: 18 August 2020 / Approved: 20 August 2020 / Online: 20 August 2020 (13:43:09 CEST)

A peer-reviewed article of this Preprint also exists.

Levitsky, V.; Oshchepkov, D.; Zemlyanskaya, E.; Merkulova, T. Asymmetric Conservation within Pairs of Co-Occurred Motifs Mediates Weak Direct Binding of Transcription Factors in ChIP-Seq Data. Int. J. Mol. Sci. 2020, 21, 6023. Levitsky, V.; Oshchepkov, D.; Zemlyanskaya, E.; Merkulova, T. Asymmetric Conservation within Pairs of Co-Occurred Motifs Mediates Weak Direct Binding of Transcription Factors in ChIP-Seq Data. Int. J. Mol. Sci. 2020, 21, 6023.

Journal reference: Int. J. Mol. Sci. 2020, 21, 6023
DOI: 10.3390/ijms21176023

Abstract

Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding to genomic DNA of at least two TFs is the widespread mechanism of transcription regulation. Cooperating TFs can be revealed through the analysis of co-occurrence of their motifs. Methods: We applied Motifs Co-Occurrence Tool (MCOT) that predicted pairs of spaced or overlapped motifs (composite elements, CEs) for a single ChIP-seq dataset. We improved MCOT capability for prediction of asymmetric CEs with one of participating motifs possessing higher conservation than another does. Results: Analysis of 119 ChIP-seq datasets for 45 human TFs revealed that almost for all families of TFs the co-occurrence with an overlap between motifs of target TFs and more conserved partner motifs was significantly higher than that for less conserved partner motifs. The asymmetry toward partner TFs was the most clear for partner motifs of TFs from ETS family. Conclusion: Co-occurrence with an overlap of less conserved motif of a target TF and more conserved motifs of partner TFs explained a substantial portion of ChIP-seq data lacking conserved motifs of target TFs. Among other TF families, conservative motifs of TFs from ETS family were the most prone to mediate interaction of target TFs with its weak motifs in ChIP-seq.

Subject Areas

chromatin immunoprecipitation followed by sequencing; transcription factors binding sites prediction; cooperative binding of transcription factors; composite elements; motifs conservation; classification of transcription factors; ETS transcription factor family; direct binding of transcription factors; overlap of motifs

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