Research On The Influencing Factors Of Transcription Factor Binding Based On ASB Events

Transcription is an important part of the gene expression process.During the development and differentiation of eukaryotic systems,transcription factors continuously and variably regulate the expression of cell-type-specific genes and determine the biological function of cells.Transcription factors regulate the corresponding genes by binding to the enhancer or promoter region of DNA,and promote or inhibit the transcription level of the gene.Its abnormal binding on DNA will cause disorder of the transcriptional regulatory network,which will affect gene expression.Exploring the influencing factors of transcription factor binding is of great significance for understanding the process of gene regulation.In this paper,based on the Allele-Specific Binding(ASB)events of transcription factors,three main factors that affect transcription factor binding are studied,including sequence variation,transcription factor co-binding,and chromatin accessibility.In this paper,we obtained multi-omics data of GM12878 and K562 cell lines,and detected and screened the heterozygous variation in the transcriptional regulatory region of the genome through the DNA-seq data of the two cell lines.At these heterozygous mutation sites,the number of Reads overlaid on the heterozygous mutation sites in the transcription factor's Ch IP-seq data was directly used to identify 9 ASB events within the binding interval of 9 transcription factors.On this basis,this paper studies the effects of sequence variation,transcription factor co-binding,and chromatin accessibility on transcription factor binding from both qualitative and quantitative aspects.In terms of qualitative research,this paper determines whether three factors can affect the binding of transcription factors through the significance test of Wilcoxon differences between groups.In terms of quantitative research,this paper uses the PWM score at the binding site to assess the effect of mutation type and position on sequence characteristics,and uses a linear model to describe the impact of changes in the binding site sequence on the binding of transcription factors;at the same time,this paper also uses a linear model The correlation of allelic differential binding between co-bound transcription factors was described,and DNase-seq data was used to study the effect of chromatin openness on transcription factor binding.The results of this study confirmed that sequence variation,transcription factor cocombination,and chromatin accessibility can all affect the binding of transcription factors on DNA;found that the type and position of sequence variation affect the transcription factor binding rules;quantitative analysis of co-binding transcription Factor binding mode and imbalance of chromatin accessibility are related to transcription factor ASB events.