Characterization of the human thyroid epigenome

• Main Author: Siu, Celia
• Language: English
• Published: University of British Columbia 2017
• Online Access: http://hdl.handle.net/2429/61000

The thyroid gland, necessary for normal human growth and development, is essential for the regulation of metabolism. Its function – to produce and secrete appropriate levels of thyroid hormone – is simple; however accurate assessment of thyroid abnormality is challenging and a fundamental understanding of the normal thyroid is therefore needed. One way to characterize the normal functioning of the thyroid gland is to study the epigenome and resulting transcriptome within its constituent cells. In this study, we compare the consistency of chromatin state annotations across the epigenomes from the grossly uninvolved tumour-adjacent thyroid tissue of four human individuals using ChIP-seq and RNA-seq. We profile four activating (H3K4me1, H3K4me3, H3K27ac, H3K36me3) and two repressing (H3K9me3, H3K27me3) histone modifications, identify chromatin states using a hidden Markov model, produce a novel metric for model selection, and establish epigenomic maps of 19 chromatin states. We found that epigenetic features characterizing promoters and transcription elongation tend to more consistent across epigenomes and that epigenetically active genes consistent across all epigenomes tend to have higher expression than those that are not marked as epigenetically active in all samples. We also identified a set of 18 genes epigenetically active and consistently expressed in the thyroid that are likely relevant to thyroid function. Altogether, we believe the epigenomes presented in this work represent a useful resource to gain a deeper understanding of the underlying molecular biology of thyroid function and provide contextual information of thyroid and human epigenomic data for comparison and integration into future studies. === Science, Faculty of === Graduate