The Regulation Of Multiple Genomic Signals On Target Genes Of Distal Enhancers In Gm12878,Hela And K562 Cell Lines

In eukaryotic cells,different genes present precise selective expression in specific cells and perform relevant biological functions.Among them,transcription factors,epigenetic modifications,3D folding patterns of the genome and so on have important roles in the selective transcriptional expression of these genes.In 3D genomics,enhancers in cis-regulatory elements can cooperatively regulate genes with close spatial distances under a combination of transcription factors and apparent modification signals.In the regulation of distal enhancer target genes,the polymorphism of enhancer regulation and the complexity of chromatin spatial structure still make researchers lack a deep understanding of the biological regulatory mechanism.Recently,due to the development of high-throughput sequencing technologies such as epigenetic omics and chromatin conformation capture,researchers are able to study the regulatory mechanism of enhancers on distal target genes,reveal the pathogenic mechanism of human diseases,and promote the development of molecular drug design.In this paper,based on the 5C and Hi-C technical databases,extracting transcription factors and epigenetics,the article studied the regulatory role of distal enhancers and target genes by using a variety of algorithmic models.The article not only found many important regulatory signatures,but also analyzed their positional properties and cell line specificity.The main research contents are summarized as follows:(1)Based on the 5C technical database,the article extracts characteristic parameter from different classes of epigenetic markers,transcription factors,and characteristic parameters of three regulatory regions,including histone modifications,transcription factors,DNase I,e RNA,DNA-methylation and nucleosome occupancy.Then,the article models the gene expression levels regulated by these signatures with distal enhancers by combining features using GBM,RF and SVR algorithms.At the same time,the article explored important features associated with distal regulation and their regulatory discrepancy between positive and negative sets.(2)Based on the 5C and Hi-C technical databases,the article explored the regulatory relationship of distal enhancers and target genes within TADs and outside TADs.In this article,we used the above three models of different regulatory regions,and transcription factors within and outside TADs to study the regulation of the expression level of distal enhancer target genes.By analyzing the regulatory role of multiple class features on target genes,we find differences in the expression levels of distal enhancers within TADs and outside of TADs,and explore important regulatory signals in specific regions,such as H3k27me3＿p,H3k36me3＿p,H3k79me2＿p and H2az＿p.(3)Since epigenetic features differ in the site distribution in the same regulatory region,to further explore the regulatory characteristics of these epigenetic features on the gene expression of enhancer targets at distal enhancers,the article segmented extracted features of histone modifications,e RNA,DNase I and DNA methylation in three regulatory regions,with the optimization and selection of the segmented features,using the combined features.It was also found that the regulation of epigenetic characteristics is somewhat site-specific.