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- Title
Characterization of universal features of partially methylated domains across tissues and species.
- Authors
Decato, Benjamin E.; Qu, Jianghan; Ji, Xiaojing; Wagenblast, Elvin; Knott, Simon R. V.; Hannon, Gregory J.; Smith, Andrew D.
- Abstract
Background: Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. Results: In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly "escapee" genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Conclusions: Our improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.
- Subjects
GENE expression; CELL lines; CANCER cells; DEFINITIONS; HUMAN genes
- Publication
Epigenetics & Chromatin, 2020, Vol 13, Issue 1, p1
- ISSN
1756-8935
- Publication type
Article
- DOI
10.1186/s13072-020-00363-7