Journal article
Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes
The FEBS journal, Vol.286(1), pp.82-109
01/2019
DOI: 10.1111/febs.14728
PMCID: PMC6326865
PMID: 30565411
Abstract
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.
Details
- Title: Subtitle
- Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes
- Creators
- Jennifer Bermick - Michigan MedicineKatherine Gallagher - Michigan MedicineAaron denDekker - Michigan MedicineSteve Kunkel - Michigan MedicineNicholas Lukacs - Michigan MedicineMatthew Schaller - Michigan Medicine
- Resource Type
- Journal article
- Publication Details
- The FEBS journal, Vol.286(1), pp.82-109
- DOI
- 10.1111/febs.14728
- PMID
- 30565411
- PMCID
- PMC6326865
- ISSN
- 1742-464X
- eISSN
- 1742-4658
- Grant note
- K12 HD028820 / NICHD NIH HHS UL1 TR002240 / NCATS NIH HHS R01 HL031237 / NHLBI NIH HHS UL1 TR000433 / NCATS NIH HHS
- Language
- English
- Date published
- 01/2019
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984353928202771
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