Study On Relationship Between The Distribution Of Histone Modifications And Gene Expression In GM12878 And K562 Cell Lines

In recent years,based on the rapid development of high-throughput sequencing technology,a massive data of epigenetics was generated.Many biological function of epigenetic modifications hided in these data.It is urgent need that biological information workers participate in how to reveal biological function of epigenetic modifications.In addition,as one of the most important epigenetic modifications,histone modification not only has a certain relationship with gene expression,but also plays a key regulatory role in the occurrence of cancer.Therefore,it is helpful to understand the mechanism of histone modification and treatment of cancer.In this work,GM12878 normal cell line and K562 cancer cell line in human blood are selected as research object.The spearman correlations between the expression levels of genes and 11 histone modifications are calculated,respectively.By clustering a number of histone modifications,a network of histone modifications in K562 cell line is constructed;partial correlation networks of 11 histone modifications are established in K562 cell line;GO function and KEGG pathway of oncogenes and tumor suppressor genes are analyzed in DAVID database.The detailed research conclusions are listed as follows:1.The distributions of 11 histone modifications in the promoter regions of oncogene and tumor suppressor gene are calculated.The results show that different histone modifications are located at different positions in promoter regions.Some histone modifications are mainly distributed the flanking sequence of the transcription start site and some histone modifications are located the down regions of the transcription start site.There are partial histones modifications are poorly distributed in the promoter region.2.The spearman correlations between histone modifications and gene expressions are computed.And four important histone modifications H3K9 ac,H3K27ac,H3K79me2 and H3K36me3 which regulate the genes is of leukemia are found.The importance of four histone modifications in regulating leukemia is also verified by the theory of multiple linear regressions.3.Based on the selected again oncogenes and tumor suppressor genes,partial correlation networks of histone modifications related to oncogenes and tumor suppressor genes are constructed in K562 cell line.The two strongly related histone modification clusters of oncogenes(H3K4me3?H3K4me2?H3K79me2?H3K9ac? H3K27ac)and(H3K4me1,H3K36me3)are revealed by clustering histone modifications.And a strongly related histone modification cluster of tumor suppressor genes(H3K4me2?H3K4me3?H2az?H3K9ac?H3K27ac?H3K79me2?H3K4me1)is built.4.GO function and KEGG pathway of oncogenes and tumor suppressor genes in DAVID database are analyzed,and their intersection with the cell identity gene regulated by the super-enhancer was selected.The four key oncogenes FOXL2?GATA1?LYL1 and TRIM24 which regulating the occurrence of leukemia and a key tumor suppressor gene PTEN regulating the genesis of leukemiais are found,respectively.