ABSTRACT
BACKGROUND: Transposons are selfish genetic elements that self-reproduce in host DNA. They were active during evolutionary history and now occupy almost half of mammalian genomes. Close insertions of transposons reshaped structure and regulation of many genes considerably. Co-evolution of transposons and host DNA frequently results in the formation of new regulatory regions. Previously we published a concept that the proportion of functional features held by transposons positively correlates with the rate of regulatory evolution of the respective genes. METHODS: We ranked human genes and molecular pathways according to their regulatory evolution rates based on high throughput genome-wide data on five histone modifications (H3K4me3, H3K9ac, H3K27ac, H3K27me3, H3K9me3) linked with transposons for five human cell lines. RESULTS: Based on the total of approximately 1.5 million histone tags, we ranked regulatory evolution rates for 25075 human genes and 3121 molecular pathways and identified groups of molecular processes that showed signs of either fast or slow regulatory evolution. However, histone tags showed different regulatory patterns and formed two distinct clusters: promoter/active chromatin tags (H3K4me3, H3K9ac, H3K27ac) vs. heterochromatin tags (H3K27me3, H3K9me3). CONCLUSION: In humans, transposon-linked histone marks evolved in a coordinated way depending on their functional roles.
Subject(s)
Chromatin/genetics , Evolution, Molecular , Histone Code , Histones/genetics , Chromatin/chemistry , Chromatin Assembly and Disassembly , DNA Transposable Elements , Histones/chemistry , Humans , Models, GeneticABSTRACT
Aim: To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. Materials & methods: XmaI-reduced representation bisulfite sequencing DNA methylation sequencing method was used to profile DNA methylation of 110 BC samples and 6 normal breast samples. Intrinsic DNA methylation BC subtypes were elicited by unsupervised hierarchical cluster analysis, and cluster-specific differentially methylated genes were identified. Results & conclusion: Overall, six distinct BC methylotypes were identified. BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated. Highly and moderately methylated superclusters, each incorporate three distinct epigenomic BC clusters with specific features, suggesting novel perspectives for personalized therapy.
Subject(s)
Breast Neoplasms/genetics , DNA Methylation , Breast Neoplasms/therapy , Cell Line, Tumor , Cluster Analysis , Epigenesis, Genetic , Female , HumansABSTRACT
AIM: To develop a reduced representation bisulfite sequencing (RRBS) approach for rapid and affordable genome-wide DNA methylation analysis. METHODS: We have selected restriction endonuclease XmaI to produce RRBS library fragments. After digestion and partial fill-in DNA fragments were ligated to barcoded adapters, bisulfite converted, size-selected, and sequenced on the Ion Torrent Personal Genome Machine. XmaI-RRBS results were compared with the previously published RRBS data. RESULTS: We have developed an XmaI-RRBS method for rapid and affordable genome-wide DNA methylation analysis, with library preparation taking only 4 days and sequencing possible within 4 h. We have also addressed several challenges in order to further improve the RRBS technology. XmaI-RRBS may be performed on degraded DNA samples and is compatible with the bench-top next-generation sequencing machines.
