Integrated RNA-seq and ChIP-seq analysis reveals a feed-forward loop regulating H3K9ac and key labor drivers in human placenta

Bingbing Wang, Panwen Wang, Nataliya Parobchak, Nathan Treff, Xin Tao, Junwen Wang, Todd Rosen

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Chromatin alterations are important mediators of gene expression changes. We have recently shown that activated non-canonical NF-κB 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-κB, 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.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalPlacenta
Volume76
DOIs
StatePublished - Jan 15 2019

    Fingerprint

Keywords

  • ChIP-seq
  • Cytotrophoblast
  • Labor drivers
  • Placenta
  • RNA-seq

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this