Journal
PLACENTA
Volume 76, Issue -, Pages 40-50Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2019.01.010
Keywords
RNA-seq; ChIP-seq; Placenta; Cytotrophoblast; Labor drivers
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Background: Chromatin alterations are important mediators of gene expression changes. We have recently shown that activated non-canonical NF-.B signaling (RelB/p52) recruits histone acetyltransferase CBP and deacetylase HDAC1 to selectively acetylate H3K9 (H3K9ac) to induce expression of corticotropin-releasing hormone (CRH) and prostaglandin-endoperoxide synthase-2 (PTGS2) in the human placenta. Both of these genes play a role in initiating parturition in human pregnancy. Methods: We performed chromatin immunoprecipitation followed by gene sequencing (ChIP-seq) in primary term human cytotrophoblast (CTB) with use of antibodies to RelB, CBP, HDAC1 and H3K9ac. We further associated these chromatin alterations with gene expression changes from mid-trimester to term in CTB by RNA sequencing (RNA-seq). Results: We detected a genome-wide differential gene enrichment between mid-trimester and term human placenta. Pathway analysis identified that cytokine-cytokine receptor interaction, NF-kappa B, and TNF are the leading pathways enriched in term placenta and associated with these chromatin alterations. Discussions: Our analysis has provided the first-time characterization of the key players of human placental origin with molecular changes resulting from chromatin modifications, which could drive human labor.
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