Investigation of gene expression and allelic imbalance in a laboratory marsupial model
Type of DegreePhD Dissertation
General Veterinary Medicine
Restriction TypeAuburn University Users
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Biallelic expression of genes in diploid organisms serves as a crucial mechanism to ensure functional redundancy in case of mutation or loss of one allele. However, exceptions to this rule exist, primarily in genes involved in genomic imprinting and sex chromosome dosage compensation via X-chromosome inactivation (XCI). Genomic imprinting is a parent-of-origin-specific expression phenomenon that occurs in the autosomes of diploid cells that plays fundamental roles in many biological processes. XCI is the process in females that one of the two X chromosomes is transcriptionally silenced to achieve X-linked gene dosage compensation during early embryonic development. In mammals, XCI and genomic imprinting are both found exclusively in therian mammals, including eutherians and marsupials. They possess a lot of common features, including cis-acting control centers and epigenetic regulations, which encompass histone modifications, differential DNA methylation, and noncoding RNAs. Compared to the extensive investigations in eutherian mammals, systematic and unbiased analysis of genomic imprinting and XCI in marsupial species is limited, which can shed light on the mechanisms and evolutionary origins of these two processes. In this dissertation, we used a well-developed marsupial model, the gray, short-tailed opossum Monodelphis domestica, to investigate the genomic imprinting and XCI phenomena, as well as the underlying regulatory mechanisms. Transcriptome-wide RNA-seq analysis was performed in samples of different tissue types and different developmental stages, from reciprocal crosses of well-characterized M. domestica genetic stocks. In addition, a gene expression analysis of M. domestica in response to environmental toxic compounds was also described. Our results in genomic imprinting describe the first unbiased survey of genomic imprinting in marsupials, which sheds light on mechanisms of epigenetic regulation and the evolution of genomic imprinting in therian mammals. The investigation on XCI fills an important knowledge gap regarding XCI in adult marsupial tissues. We also conducted the first study to investigate the effect of PFASs in a marsupial model, providing supportive evidence for significant transcriptomic alterations and suggesting that this marsupial model may serve as a biomedical model for exploring the potential toxicity in environmental toxic compounds.