Partially methylated domains are hallmarks of a cell specific epigenome topology

Salhab, A.; Nordström, K.; Kattler, K.; Ebert, P.; Ramirez, F.; Arrigoni, L.; Müller, F.; Cadenas, C.; Hengstler, J.; Lengauer, T.; Manke, T.; DEEP Consortium,; Walter, J.

doi:10.1101/249334

bioRxiv · 10.1101/249334

Partially methylated domains are hallmarks of a cell specific epigenome topology

Salhab, A.·Nordström, K.·Kattler, K.·Ebert, P.·Ramirez, F.·Arrigoni, L.·Müller, F.·Cadenas, C.·Hengstler, J.·Lengauer, T.·Manke, T.·DEEP Consortium,·Walter, J.

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Abstract

BackgroundPartially methylated domains, PMDs, are extended regions in the genome exhibiting a reduced average DNA-methylation level. PMDs cover gene-poor and transcriptionally inactive regions and tend to be heterochromatic. Here, we present a first comprehensive comparative analysis of PMDs across more than 190 WGBS methylomes of human and mouse cells providing a deep insight into structural and functional features associated with PMDs.\n\nResultsPMDs are ubiquitous signatures covering up to 75% of the genome in human and mouse cells irrespective of their tissue or cell origin. Additionally, each cell type comes with a distinct set of specific PMDs, and genes expressed in such PMDs show a strong cell type effect. Demethylation strength varies in PMDs with a tendency towards a more pronounced effect in differentiating and replicating cells. The strongest demethylation is observed in highly proliferating and immortal cancer cell lines. A decrease of DNA-methylation within PMDs tends to be linked to an increase in heterochromatic histone marks and a decrease of gene expressions. Characteristic combinations of heterochromatic signatures in PMDs are linked to domains of early, middle and late DNA-replication.\n\nConclusionPMDs are prominent signatures of long-range epigenomic organization. Integrative analysis identifies PMDs as important general, lineage- and cell-type specific topological features. PMD changes are hallmarks of cell differentiation. Demethylation of PMDs combined with increased heterochromatic marks is a feature linked to enhanced cell proliferation. In combination with broad histone marks PMDs demarcate distinct domains of late DNA-replication.

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Salhab, A., Nordström, K., Kattler, K., Ebert, P., Ramirez, F., Arrigoni, L., Müller, F., Cadenas, C., Hengstler, J., Lengauer, T., Manke, T., DEEP Consortium,, Walter, J.. 2018-01-17. Partially methylated domains are hallmarks of a cell specific epigenome topology. https://doi.org/10.1101/249334

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