Detection of cytosine and CpG density in proto-oncogenes and tumor suppressor genes in promoter sequences of acute myeloid leukemia

Abstract

Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia. The promoter sequences were divided into a 100 nucleotide window from -500 to +100 nucleotides and 20 nucleotide window from -100 to +100. Each window is analyzed to find the higher C type and CpG islands density, which may cause the increased methylation in the promoter sequence. Our novel findings show that promoter sequence cytosine repeats and CpG density increase closer to transcription sites, especially just before and after the transcription start site (TSS). The results demonstrate that cytosine density increases while proto-oncogenes and TSG promoter sequences are closer to TSS 50.8% and 41.0% respectively, if (-500 to -200) and (-100 to +100) windows of the nucleotide sequences are compared. This proves that around TSS location has special nucleotide motifs and could be an important implication for our understanding of potential methylating locations in promoters.

Single nucleotide variation catalogue from clinical isolates mapped on tertiary and quaternary structures of ESX-1 related proteins reveals critical regions as putative Mtb therapeutic targets

“…In the isolates with two silent SNPs in espI, a repeat of 6 cytosines is formed. In cancer, this type of motif has been linked to changes in methylation (Dogan et al 2017). Long PacBio reads could provide information about whether these mutations affect the methylation state of ESX-1.…”

Untitled

“… AT-hook is a DNA binding domain [19].  CxxC motif recognizes unmethylated CpG dinucleotides [20][21][22]. PHD is transcriptional coactivators [23].…”

Activation of Macrophages by CpG DNA and LPS: an FTIR Spectroscopic Study

“…They have a high structural and functional plasticity that allows them to continually inspect the body and respond to challenges in it [17][18][19]. An intriguing challenge is bacterial DNA containing unmethylated CpG oligodeoxynucleotides (CpG DNA) [20,21]. CpG DNA o f 1 7 triggers the proliferation of macrophages, the production of pro-inflammatory cytokines and chemokines, the induction of Th1 reactions, the repression of Th2 reactions, the activation of antigen-presenting cells and the proliferation of B cells [22].…”