Levitsky Victor G, Raditsa Vladimir V, Tsukanov Anton V, Mukhin Aleksey M, Zhimulev Igor F, Merkulova Tatyana I
Department of System Biology, Institute of Cytology and Genetics, Novosibirsk 630090, Russia.
Department of Natural Science, Novosibirsk State University, Novosibirsk 630090, Russia.
Int J Mol Sci. 2025 Jan 4;26(1):386. doi: 10.3390/ijms26010386.
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 ChIP-seq and 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.
转录因子（TFs）是真核基因表达的主要调节因子。至少两个转录因子与基因组DNA的协同结合是转录调控的主要机制。对ChIP-seq实验中研究的不同靶标转录因子的过表达基序对共现情况进行大规模分析，可以阐明转录因子协同作用的机制。我们根据ChIP-seq和ChIP-seq/DAP-seq实验中靶标转录因子的DNA结合结构域（DBD）结构将其分类。我们研究了基序的同型对，每个基序使用相同的识别模型。不对称和对称对由具有远亲和近亲和识别分数的基序组成。我们发现，所有转录因子类别中，不对称基序对占主导。来自小鼠/植物“碱性螺旋-环-螺旋（bHLH）”、“碱性亮氨酸拉链（bZIP）”和“色氨酸簇”类别的转录因子以及小鼠“p53结构域”和“Rel同源区域”类别的转录因子，其不对称同型基序对的富集程度最高。先锋转录因子尽管其DBD类型不同，但与其他转录因子相比，在同型基序对内具有更高的不对称性显著性。同型顺式元件内的不对称性是解读基因转录调控机制的一个有前景的新特征。
