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Epigenetic mechanisms underlying the influence of paternal drug experience on offspring behavior

Periodic Reporting for period 1 - EPOFFSPRING (Epigenetic mechanisms underlying the influence of paternal drug experience on offspring behavior)

Reporting period: 2017-03-01 to 2019-02-28

The effect of paternal environmental impacts on psychology and related diseases of babies has been concern of the public. Those impacts include pollution, stress, nicotine intaking, alcohol consumption and so on. Such an idea of transmitting paternal environmental impact across generations has been indicated and described in studies across species, but the mechanism is still unclear. The overall aim of the project was to test whether H3K27me3, a type of epigenetic modification on histone 3 influencing gene expression, is involved in transmitting environmental impact across generation to influence the behavior of offspring. With a behavioral neuroscience background, the experienced research (ER) applied his expertise in high throughput behavioral assay and combined techniques he learned from the host lab, including epigenetic profiling, next generation sequencing, targeted epigenome editing and computational analysis to address specifically whether paternal drug experience influenced offspring behavior via modifying H3K27me3 on dopamine-related genes that are involved in various behaviors. Besides advancing our understanding of the importance and mechanism of paternal inheritance and the role of epigenetics in general, this project would also further extend zebrafish as a model in studying cross-generational transmission of environmental experience by combining multidisciplinary techniques. The trainings ER received would be beneficial and essential for his future goal to study epigenetic mechanisms underlying physiology and pathology of brain.
During the two months of the fellowship, work performed include three parts. Firstly, the ER has learned and optimized experimental protocols to quantify H3K27me3 enrichment from small-sized biological material, which is essential for evaluating the effects of paternal environmental stress on H3K27me3 enrichment of baby’s genome. Secondly, the ER has successfully developed CRIPR/Cas9 system in the host lab. Thirdly, the ER has successfully designed and engineered genetic tools for manipulating (upregulating and downregulating respectively) H3K27me3 on specific genes, which is essential for tesingt whether paternal environmental stress induced effects on H3K27me3 of baby’s gene are sufficient and necessary for baby’s psychological phenotype.
The progress so far will be the basis for testing paternal environmental stress induced effect on baby’s H3K27me3 and its causal relationship with baby’s behavioral alterations. Throughout the training, the ER have gained technique and basic knowledge on epigenetics and established relationship with colleagues in the field of genetics and epigenetics, he will benefit from those for his future career as a neuroscientist focusing on genetics and epigenetics. Furthermore, the CRISPR/Cas9 established during the fellowship will be further used in the lab. Especially, the dCas9 based targeted epigenetic modification project is currently continued by other lab-members and the dCas9-basis targeted DNA binding is being extended to image developmental genetic events in the lab.