TY - JOUR

T1 - Asymmetry of Motif Conservation Within Their Homotypic Pairs Distinguishes DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data

AU - Levitsky, Victor G.

AU - Raditsa, Vladimir V.

AU - Tsukanov, Anton V.

AU - Mukhin, Aleksey M.

AU - Zhimulev, Igor F.

AU - Merkulova, Tatyana I.

N1 - This study was supported by budget project FWNR-2022-0020 of the Institute of Cytology and Genetics of SB RAS.

PY - 2025/1/4

Y1 - 2025/1/4

N2 - Transcription factors (TFs) are the main regulators of eukaryotic gene expression. The cooperative binding of at least two TFs to genomic DNA is a major mechanism of transcription regulation. Massive analysis of the co-occurrence of overrepresented pairs of motifs for different target TFs studied in ChIP-seq experiments can clarify the mechanisms of TF cooperation. We categorized the target TFs from M. musculus ChIP-seq and A. thaliana ChIP-seq/DAP-seq experiments according to the structure of their DNA-binding domains (DBDs) into classes. We studied homotypic pairs of motifs, using the same recognition model for each motif. Asymmetric and symmetric pairs consist of motifs of remote and close recognition scores. We found that asymmetric pairs of motifs predominate for all TF classes. TFs from the murine/plant ‘Basic helix–loop–helix (bHLH)’, ‘Basic leucine zipper (bZIP)’, and ‘Tryptophan cluster’ classes and murine ‘p53 domain’ and ‘Rel homology region’ classes showed the highest enrichment of asymmetric homotypic pairs of motifs. Pioneer TFs, despite their DBD types, have a higher significance of asymmetry within homotypic pairs of motifs compared to other TFs. Asymmetry within homotypic CEs is a promising new feature decrypting the mechanisms of gene transcription regulation.

AB - Transcription factors (TFs) are the main regulators of eukaryotic gene expression. The cooperative binding of at least two TFs to genomic DNA is a major mechanism of transcription regulation. Massive analysis of the co-occurrence of overrepresented pairs of motifs for different target TFs studied in ChIP-seq experiments can clarify the mechanisms of TF cooperation. We categorized the target TFs from M. musculus ChIP-seq and A. thaliana ChIP-seq/DAP-seq experiments according to the structure of their DNA-binding domains (DBDs) into classes. We studied homotypic pairs of motifs, using the same recognition model for each motif. Asymmetric and symmetric pairs consist of motifs of remote and close recognition scores. We found that asymmetric pairs of motifs predominate for all TF classes. TFs from the murine/plant ‘Basic helix–loop–helix (bHLH)’, ‘Basic leucine zipper (bZIP)’, and ‘Tryptophan cluster’ classes and murine ‘p53 domain’ and ‘Rel homology region’ classes showed the highest enrichment of asymmetric homotypic pairs of motifs. Pioneer TFs, despite their DBD types, have a higher significance of asymmetry within homotypic pairs of motifs compared to other TFs. Asymmetry within homotypic CEs is a promising new feature decrypting the mechanisms of gene transcription regulation.

KW - chromatin immunoprecipitation followed by sequencing

KW - classification of transcription factors

KW - conservation of motifs

KW - cooperative binding of transcription factors

KW - direct binding of transcription factors

KW - transcription factor binding site prediction

UR - https://www.mendeley.com/catalogue/a6c595d8-cdc8-3a17-8ea8-d4ffe0389da5/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85214536141&origin=inward&txGid=6b9056e729246307debcf88599463c11

U2 - 10.3390/ijms26010386

DO - 10.3390/ijms26010386

M3 - Article

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 386

ER -