Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Asymmetry of Motifs Conservation within Homotypic Composite Elements Differentiates DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data

Version 1 : Received: 24 November 2023 / Approved: 24 November 2023 / Online: 27 November 2023 (07:26:54 CET)

How to cite: Levitsky, V. G.; Raditsa, V. V.; Tsukanov, A.; Mukhin, A. M.; Merkulova, T. I. Asymmetry of Motifs Conservation within Homotypic Composite Elements Differentiates DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data. Preprints 2023, 2023111617. https://doi.org/10.20944/preprints202311.1617.v1 Levitsky, V. G.; Raditsa, V. V.; Tsukanov, A.; Mukhin, A. M.; Merkulova, T. I. Asymmetry of Motifs Conservation within Homotypic Composite Elements Differentiates DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data. Preprints 2023, 2023111617. https://doi.org/10.20944/preprints202311.1617.v1

Abstract

(1) Background: Transcription factors (TFs) are main regulators of eukaryotic gene expression. The cooperative binding of at least two TFs to genomic DNA is the widespread mechanism of transcription regulation. Massive analysis of co-occurrence of overrepresented pairs of motifs (composite elements, CEs) for different target TFs studied in ChIP-seq experiments can clarify the mechanisms of TF cooperation. (2) Methods: We focused on homotypic CEs representing the same motif models and considered only CEs with spacers. We improved the capability of the Motifs Co-Occurrence Tool (MCOT) to predict asymmetric homotypic CEs in which one of par-ticipating motifs has higher conservation than the other. We categorized the target TFs from the data of M. musculus ChIP-seq and A. thaliana ChIP-seq/DAP-seq according to the structure of DNA-binding domains (DBDs) into classes. (3) Results: For all TF classes the predominance of asymmetric CEs over both symmetric and those with no enrichment in both directions was re-vealed. Target TFs from classes Basic helix-loop-helix factors (bHLH) and Basic leucine zipper factors (bZIP) showed the highest fractions of datasets with asymmetric CEs. We showed that pioneer TFs, despite their DBD types, have a higher significance of asymmetry within homotyp-ic CEs compared to other TFs. (4) Conclusion: Asymmetry within homotypic CEs is a promising new feature decrypting the mechanisms of gene transcription regulation.

Keywords

Chromatin immunoprecipitation followed by sequencing; transcription factors binding sites prediction; cooperative binding of transcription factors; motifs conservation; classification of transcription factors; direct binding of transcription factors

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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