Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease

Bo Zhang, M. Yvonne Kim, Gi Nell Elliot, Yan Zhou, Guangfeng Zhao, Daofeng Li, Rebecca F. Lowdon, Matthew Gormley, Mirhan Kapidzic, Joshua F. Robinson, Michael T. McMaster, Chibo Hong, Tali Mazor, Emily Hamilton, Renee L. Sears, Erica C. Pehrsson, Marco A. Marra, Steven J.M. Jones, Misha Bilenky, Martin HirstTing Wang, Joseph F. Costello, Susan J. Fisher

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 decreased across the genome as pregnancy advanced. Cytotrophoblasts from severe preeclampsia had substantially increased H3K27 acetylation globally and at genes that are normally downregulated at term but upregulated in this syndrome. In addition, some cases had an immature pattern of H3K27ac peaks, and others showed evidence of accelerated aging, suggesting subtype-specific alterations in severe preeclampsia. Thus, the cytotrophoblast epigenome dramatically reprograms during pregnancy, placental disease is associated with failures in this process, and H3K27 hyperacetylation is a feature of severe preeclampsia.

Original languageEnglish
Pages (from-to)1238-1252.e5
JournalDevelopmental cell
Volume56
Issue number9
DOIs
StatePublished - May 3 2021

Keywords

  • DNA methylation
  • H3K27ac
  • H3K9me3
  • chorionic villi
  • cytotrophoblast
  • gestational regulation
  • histone modification
  • human placenta
  • placental disease
  • preeclampsia

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