The Effect Of CTCF Binding And DNA Methylation On Histone Modification Distribution

The polyfunctional regulator CTCF plays a central role in complex biological processes,including transcription,imprinting and subnuclear localization.Moreover,CTCF activity,especially its DNA-binding activity,can be altered by various factors,including DNA methylation.Histone modification,which is an important content of epigenetics research,is associated with gene expression and genome function by establishing global chromatin environments.With the high-throughput sequencing development,a large number of databases have been provided to study the association between transcription factor CTCF binding and DNA methylation,as well as their effect on histone modifications.In the study,GM12878 and K562 cell lines from human blood tissues were obtained from the ENCODE Consortium.Based on the hg19 RefSeq gene annotations from the UCSC website browser,12207 non-overlapping genes within 20kb upstream and downstream regions of transcription start sites were extracted.Then,the association strength named Aij between the transcription factor CTCF and genes and DNA methylation level named Mij around transcription start sites were calculated.The results indicated that there is a certain competitive relationship between Aij and Mij,and DNA methylation may prevent CTCF binding at some sequence elements.Next,we classified 12207 genes into four gene sets according to the value or Aij ana Mij,ana anaiyziea the distribution of(?)histone modifications within 3800bp in the flanking regions of transcription start sites in four gene sets respectively.The results showed that H2AFZ,H3K4me2,H3K4me3,H3K9ac,H3K27ac and H3K79me2 exhibited bimodal distributions,with the highest signal distributions in GM_? and K_? sets and the lowest in GM_? and K_? sets,which indicated that CTCF binding and DNA methylation had some effect on the distribution of histone modifications.Other five histone modifications exhibited no obvious characteristics,and had lower signal distribution.It suggested that CTCF binding and DNA methylation had little effect on their distributions.Finally,the gene expression level RPKM was calculated by a DEGseq package of R language,as well as the correlation between RPKM and Aij or Mij in three gene sets of two cell lines.The results illustrated that DNA methylation level around transcription start sites was negatively weak correlated with gene expression in some degree,but the CTCF binding was positively weak correlated with gene expression.