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

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.

journal_name

Placenta

journal_title

Placenta

authors

Wang B,Wang P,Parobchak N,Treff N,Tao X,Wang J,Rosen T

doi

10.1016/j.placenta.2019.01.010

subject

Has Abstract

pub_date

2019-01-15 00:00:00

pages

40-50

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(18)31075-0

journal_volume

76

pub_type

杂志文章

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