International Journal of Medicine and Data

Chronic myelogenous leukemia (CML) is a malignant clonal disease of hematopoietic stem cells, and studies have shown that the progression of CML is associated with abnormal histone modification (HM) patterns. Here, we explored the relationship between H3K79me2 intensities in the gene body region and gene expression changes. The results exhibited that the binding intensities of H3K79me2 in the normal cells were negatively correlated with gene expression changes beyond the regulatory mechanisms that have been discovered (ρ=-0.81, P<0.01). Specifically, the expression levels of gene with low H3K79me2 binding intensities changed significantly, while the expression levels of gene with high H3K79me2 binding intensities changed little during carcinogenesis. Regulatory element analysis displayed that transcription factors GATA3, GATA4, TEAD1, TEAD3, TEAD4 and TRPS1 promoted the up-regulation of genes with low H3K79me2 intensities (ρ=0.95, P<0.01), and transcription factors Ascl2, E2A, IRF3, IRF4, Oct4 and ZEB2 induced the down-regulation of genes with low H3K79me2 binding abundance (ρ=0.97, P<0.01). Further analysis revealed that H3K79me2 intensities negatively regulated gene expression changes regardless of gene expression levels and gene lengths. Finally, Pathway enrichment analyses showed that genes with low H3K79me2 intensities were involved in leukemia-related signaling pathways, such as regulation of leukocyte migration, regulation of cell adhesion. These conclusions suggested that lower gene-body H3K79me2 intensities may be closely related to the occurrence of CML.

Chronic myelogenous leukemia; Histone modification; H3K79me2; Gene expression changes