Palmer, Andrew (2024) Fibre Type Specific DNA Methylation in Human Skeletal Muscle. PhD thesis, Victoria University.

Abstract

Skeletal muscle is a heterogeneous tissue comprised of diverse cell types and is highly adaptable and sensitive to stimuli, such as exercise. Epigenetics is the study of mechanisms that impact chromosomal regions to alter gene activity without an underlying change in the sequence of Deoxyribonucleic acid (DNA). One of the most widely studied epigenetic mechanisms is DNA methylation (DNAm), which plays an important role in perpetuating cell identity. To date, studies have shown that exercise causes widespread DNAm changes in skeletal muscle. However, these studies have remained at the whole tissue-level. This approach limits interpretation of results due to, 1) the influence of cell identities on DNAm, 2) the variable cellular composition of tissue and 3) the specific responses of each cell type to exercise. This thesis investigates the genome-wide DNAm profiles of Type I, Type IIa and Type IIx multi-nucleated muscle fibres from human muscle at baseline and after twelve weeks of High Intensity Interval Training (HIIT). It describes the development of a novel method for the simultaneous extraction of DNA and protein from pooled human skeletal muscle fibre fragments (Chapter 4). The thesis also compares the methylome and proteome assessed in skeletal muscle fibre types using the same biological samples (Chapter 5 & 6), and in response to twelve weeks of HIIT (Chapter 7). This research will contribute to a deeper understanding of fibre-type specific muscle biology and molecular adaptations to exercise, with potential to improve treatment strategies for muscle related diseases and maintenance of muscle health.

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