Application Of Bioinformatics In Epigenetics

Both genes and the environment affect a person's risk of disease.Although genes are often classified,disrupted,activated,and turned off,research on environmental exposures cannot be ignored.Environmental exposure refers to physical,biological,and physical factors that come into contact with the body in a specific time and space.Previous studies have found that genetic mutations explain about 10-15% of the pathogenesis of Parkinson's disease(PD),but environmental exposure is the main cause of most PD cases.Environmental exposure can cause mitochondrial dysfunction in the body.Mitochondrial dysfunction is a common way to induce degeneration of dopaminergic neurons,which proves that mitochondrial dysfunction is the key to induce Parkinson's disease,but its underlying mechanism is still unclear.In this chapter,we demonstrated through high-throughput sequencing methods that neurotoxin exposure or gene mutation may work together to increase H3.2 variant(H3.2 K27ac)lysine 27 acetylation and H3K27 hyperacetylation.Opening the active enhancer activity in this region causes mitochondrial dysfunction,which leads to the changes in the transcriptome and induces disease.We treated N27 cells separately by rotenone environment exposure and TFAM gene knockout.And we found from Ch IP-seq and RNA-Seq sequencing data that 509 and 619 genes were shared respectively in up-regulated and down-regulated genes,most of which were focused on biological pathways such as transcriptional regulation and signaling.To integrate RNA-seq and Ch IP-seq data,additionally we discoveried that in mitochondrial-damaged N27 cells,the increase of H3K27 ac was significantly positively correlated with the promotion of transcription.At several genomic sites,changes in H3K27 ac are consistent with transcriptional changes,indicating that m RNA expression levels induced by our mitochondrial damage model are extremely sensitive to changes in H3K27 ac modification.Also,through motif analysis,multiple transcription factors were successfully predicted,which provided targets for further experimental verification and mechanism research.Bisphenol a(BPA),as an environmental endocrine disruptor,has weak estrogen and antiandrogenic activity.And it can affect the synthesis and secretion of endogenous hormones in the body,and physiological effects in target organs,which has a negative impact on health.This chapter explores the effects of high and low doses of BPA exposure on proliferation and the specific biological pathways involved by mouse embryonic stem cell models.We confirmed that in the low-dose BPA exposure treatment group,the main influences were focused on the intermediary fiber biological processes,neural system development,cell differentiation,ion transport,multicellular biological development and cell-cell signal transduction,and sac transportation.And in the high-dose BPA treatment group,they mainly focused on ion transport,mucin connection,synaptic function,axon function,and Pol II binding.High-throughput sequencing and a variety of cross-disciplines methods provide stronger evidence for stem cell proliferation studies under BPA exposure.