RESUMO
While CpG dinucleotides are significantly reduced compared to other dinucleotides in mammalian genomes, they can congregate and form CpG islands, which localize around the 5' regions of genes, where they function as promoters. CpG-island promoters are generally unmethylated and are often found in housekeeping genes. However, their nucleotide sequences and existence per se are not conserved between humans and mice, which may be due to evolutionary gain and loss of the regulatory regions. In this study, human and rhesus monkey genomes, with moderately conserved sequences, were compared at base resolution. Using transcription start site data, we first validated our methods' ability to identify orthologous promoters and indicated a limitation using the 5' end of curated gene models, such as NCBI RefSeq, as their transcription start sites. We found that, in addition to deamination mutations, insertions and deletions of bases, repeats, and long fragments contributed to the mutations of CpG dinucleotides. We also observed that the G + C contents tended to change in CpG-poor environments, while CpG content was altered in G + C-rich environments. While loss of CpG islands can be caused by gradual decreases in CpG sites, gain of these islands appear to require two distinct nucleotide altering steps. Taken together, our findings provide novel insights into the process of acquisition and diversification of CpG-island promoters in vertebrates.
Assuntos
Ilhas de CpG , Metilação de DNA , Epigênese Genética , Genoma , Regiões Promotoras Genéticas , Animais , Sequência de Bases , Variação Genética , Genoma Humano , Genômica/métodos , Humanos , Mutação INDEL , Macaca mulatta , Mamíferos/genética , Camundongos , Mutação , Sequências Reguladoras de Ácido Nucleico , Sítio de Iniciação de TranscriçãoRESUMO
A UV-cleavable supramolecular cross-linker was designed to effectively control the mechanical strength of photocurable resin plastics. The resin monomer-soluble polyrotaxane (PRX) cross-linker was synthesized by introducing a hydrophobic n-butyl group and a cross-linkable methacrylate group in α-cyclodextrin threading to a polyethylene glycol containing UV-cleavable end groups. The UV-cleavable PRX cross-linker was completely dissolved in 2-hydroxyethytl methacrylate (HEMA) and camphorquinone, representative photocurable resin components. The dumbbell-like stiff resin plastic was prepared by irradiating the mixture with 450 nm blue light. The stiffened resin plastic maintained its ultimate tensile strength (UTS) under visible light irradiation. However, the UTS of the resin plastic was remarkably decreased to 40% of the original value once the plastic was exposed to 254 nm UV light. This indicates that the suggested UV-cleavable PRX cross-linker is effective in modulating the mechanical strength of photocurable resin plastics.