biostudies-literatureZhang BEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSNIDA NIH HHSNIEHS NIH HHSNHGRI NIH HHSNCI NIH HHSNational Institutes of Health1238-1252.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC8650129biostudies-literatureUnknown56(9)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 teDevelopmental cellHuman placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.PMC8650129U24 ES026699U24 HG012070P50HD055764R01 ES024992U01ES017154R37HD076253U01 HG009391U01 CA2000605R25DA027995P50 HD055764R25 DA027995R37 HD076253U01 ES017154R01 HD092419R01 HG007354R01HD092419R01 HG007175U41 HG010972Li DHamilton EKim MYElliot GLowdon RFFisher SJZhou YMazor TGormley MHong CSears RLBilenky MRobinson JFMcMaster MTMarra MAHirst MWang TZhao GJones SJMCostello JFZhang BKapidzic MPehrsson ECfalseHuman placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.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 te2021-01-01T00:00:00Z2021 May2026-05-31T01:07:19.415Z2025-04-04T11:31:28.688ZS-EPMC86501293389189910.1016/j.devcel.2021.04.001