Yiqin Gao - Relating Cell State Dependent Methylation to the DNA Sequence and 3D Genome

Professor Gao first introduced the effects of DNA deformation and sequence on their distribution in the genome. Based on the analysis of changes in CpG density sites where the transcription initiates, they speculated that the composition and distribution of dinucleotides might influence gene regulation mechanisms. After analyzing dinucleotide sequences around promoters and on gene bodies, they observed different characteristics in CpG density among housekeeping genes, genes of developmental and neural functions, and tissue-specific genes. These sequence differences were found to affect the binding of H1 histones. Subsequently, they examined the hierarchical distribution of CpG in the human genome and the hierarchical chromatin structure, showing that CpG could serve as a better indicator of chromatin segregation than other sequential properties. They also introduced their newly developed CTG method, which was used to analyze changes in chromatin structure during cancer development. This analysis was integrated with genomic mutation information, methylation data, and other epigenetic information to identify differences in copy number variation and chromatin structure among different types of cancer. These analyses suggest that dinucleotides and their distribution may have a broad range of effects. For example, the changes in DNA methylation during carcinogenesis are closely linked to multiscale CpG density and chromatin structure.