Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

J Bermick, K Gallagher, A denDekker… - The FEBS …, 2019 - Wiley Online Library
J Bermick, K Gallagher, A denDekker, S Kunkel, N Lukacs, M Schaller
The FEBS journal, 2019Wiley Online Library
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 Ch IP‐seq and RNA‐seq to evaluate the impact of chorioamnionitis …
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
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