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H4K16ac mediated transposable over expression leads to inflammation in Preeclampsia
Manthan Patel  1@  , Ahmed S Ali  2  , Adrianna Dabrowska  3  , Ioannis Sarropoulos  4  , Fanny Boulet  5  , Ajay Kumar Sinha  6, 7  , Pradeepa Madapura M  6  
1 : PDRA, First Author
Blizard Institute 4 Newark Street, E1 2AT -  United Kingdom
2 : First Author
Assiut University Children Hospital, Assiut University, Assiut -  Egypt
3 : Research Assistant
Blizard Institute E1 2AT -  United Kingdom
4 : Researcher
Welcome Sanger Institute, Cambridge -  United Kingdom
5 : PDRA
Blizard Institute E1 2AT -  United Kingdom
6 : Corresponding author, Group leader,
Blizard Institute E1 2AT -  United Kingdom
7 : Neonatal Consultant
Neonatal Unit, Royal London Hospital, Barts Health NHS Trust, London -  United Kingdom

Preeclampsia (PE) is a pregnancy-associated hypertension disorder which affects 5–10% of pregnant women each year worldwide. Here, we aimed to investigate the epigenetic mechanisms contributing to preeclampsia by genome-wide profiling of histone acetylations and transcriptome in healthy and preeclamptic placenta. We found a specific increase in acetylation level at histone H4 lysine 16 (H4K16ac) across transposable elements in preeclamptic placenta compared to control. H4K16ac hyperacetylation in pre-eclampsia is associated with increased transcript levels of endogenous retrovirus (ERV/LTR) and long interspersed nuclear element 1 (L1, LINE1) subfamilies of TEs in PE placenta from independent pregnancy cohorts. Furher, analysis of the additional cohorts alongwith this study, we discover upregulation of the LTR and L1 subfamilies as well as type I interferon (IFN) responsive genes upregulated in Preecalmpsia. These findings were consistent with the validation using RT-qPCR for the L1 ORF and 5' UTR as well as IFN-genes, indicating the contribution of H4K16ac-mediated upregulation TE contrbuting to inflammation in PE.


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