Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes.
chorioamnionitis
epigenetics
histone modification
monocyte
transcription
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
15
05
2018
revised:
24
08
2018
accepted:
08
12
2018
pubmed:
20
12
2018
medline:
10
7
2019
entrez:
20
12
2018
Statut:
ppublish
Résumé
Chorioamnionitis is an intrauterine infection involving inflammation of the chorion, amnion, and placenta. It leads to a fetal systemic inflammatory response that can alter the transcription of neonatal immune genes. We have previously shown that neonatal monocytes gain the activating histone tail modification H3K4me3 at promoter sites of immunologically important genes as development progresses from preterm neonate to adult. In this study, we applied ChIP-seq and RNA-seq to evaluate the impact of chorioamnionitis on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development. Chorioamnionitis exposure in neonatal monocytes resulted in a net increase in total monocyte H3K4me3, primarily in introns and intergenic regions. Immune gene expression was decreased in chorioamnionitis-exposed monocytes, with the majority of enriched transcripts falling into pathways that are not linked to the immune system. Over half of all neonatal monocyte H3K4me3 peaks, independent of their location, were associated with active gene transcription. Overall, chorioamnionitis exposure resulted in the global remodeling of the neonatal monocyte H3K4me3 landscape and changes in the expression of known immune genes. These changes resulted in a less robust inflammatory response upon exposure to a secondary challenge, which may explain why chorioamnionitis-exposed neonates have an increased risk of sepsis. DATABASE: ChIP-seq data for U30/O30/Term: GEO GSE81957 ChIP-seq data for U30C/O30C/TermC: GEO GSE111873 RNA-seq data for U/L/CU/CL: GEO GSE111927.
Identifiants
pubmed: 30565411
doi: 10.1111/febs.14728
pmc: PMC6326865
mid: NIHMS1002061
doi:
Substances chimiques
Biomarkers
0
Histones
0
histone H3 trimethyl Lys4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-109Subventions
Organisme : NICHD NIH HHS
ID : K12 HD028820
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL031237
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002240
Pays : United States
Informations de copyright
© 2018 Federation of European Biochemical Societies.
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