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Cytotrophoblast epigenome dynamics over gestation reveal aberrations in placental disease

Abstract

The human placenta and its specialized cytotrophoblasts rapidly develop, have a compressed lifespan, govern pregnancy outcomes and program the offspring’s health. Understanding the molecular underpinnings of these behaviors informs development and disease. Profiling the extraembryonic epigenome and transcriptome during the 2nd and 3rd trimesters, revealed H3K9 trimethylation overlapping deeply DNA hypomethylated domains with reduced gene expression, and compartment-specific patterns that illuminated their functions. Cytotrophoblast DNA methylation increased and several key histone modifications were lost as pregnancy advanced. Cytotrophoblasts from severe preeclampsia showed substantially increased H3K27 acetylation globally and at genes that are normally downregulated at term but upregulated in this syndrome. Thus, the cytotrophoblast epigenome rapidly reprograms during pregnancy, placental disease is associated with failures in this process, and H3K27 hyperacetylation is a feature of severe preeclampsia.

Data visulization

The visulization of palcenta epigenome can be found at WashU Epigenome Browser through folloing link: https://epigenomegateway.wustl.edu/browser/?genome=hg19&hub=https://remc.wustl.edu/dli/placenta_hub/hub

Copyright (c) 2020, Zhang Laboratory, Wang Laboratory and Costello Laboratory. Distributed under terms of the MIT License.

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