Epigenetic modification via H3K4me3 and H3K9ac in human placenta is reduced in preeclampsia

Meister, Sarah; Hahn, Laura; Beyer, Susanne; Kühn, Christina; Jegen, Magdalena; Schönfeldt, Viktoria von; Corradini, Stefanie; Schulz, Christian; Kolben, T; Hester, Anna; Appelt, Tamara; Mahner, Sven; Jeschke, Udo

doi:10.1016/j.jri.2021.103287

Cited by 12 publications

(16 citation statements)

References 35 publications

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“…However, many genes with deregulated expression were not associated with DNA methylation raising the possibility of altered chromatin signatures leading to abnormal gene expression in this placental disorder (Leavey et al, 2018). Indeed, upregulated expression of LncRNA by increased H3K4me3 has been observed in preeclampsia placentas (Sun et al, 2020), and the levels of H3K4me3 as detected by immunocytochemistry are decreased (Meister et al, 2021). Until now the connection between sperm chromatin and placenta function has been unexplored.…”

Section: Discussionmentioning

confidence: 99%

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

Pépin

Lafleur

Lambrot

et al. 2021

Preprint

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Parental environmental exposures can strongly influence descendant risks for adult disease. Metabolic disorders arise from the intersection of environmental and genetic risk factors, with epigenetic inheritance being at the center of the familial cycle of transgenerational disease. How paternal high-fat diet changes the sperm chromatin leading to the acquisition of metabolic disease in offspring remains controversial and ill-defined. Using a genetic model of epigenetic inheritance, we investigated the role of histone H3 lysine 4 methylation (H3K4me3) in the paternal transmission of metabolic dysfunction. We show that obesity-induced alterations in sperm H3K4me3 associated with offspring phenotypes and corresponded to embryonic and placental chromatin profiles and gene expression. Transgenerational susceptibility to metabolic disease was only observed when grandsires had a pre-existing genetic predisposition to metabolic dysfunction that was associated with enhanced alterations to sperm H3K4me3. This non-DNA based knowledge of inheritance has the potential to improve our understanding of how environment shapes heritability and may lead to novel routes for the prevention of disease.

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Section: Discussionmentioning

confidence: 99%

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

Pépin

Lafleur

Lambrot

et al. 2021

Preprint

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“…Along with the progression of atherosclerosis, H3K4 methylation accumulates in SMCs; H3K9ac and H3K27ac are also enriched in atherosclerotic SMCs and macrophages, thus supporting the elevated HAT activity of GCN5-like protein 1 and HAT KAT8 (89). Additionally, H3K9ac accumulates in atherosclerotic plaques in ECs (90). Furthermore, in adult heart diseases, SMYD1 is elevated to restrict hypertrophic growth by directly repressing a group of hypertrophy-associated genes, including TGFβ3 and NPPA (92).…”

Section: Histone Methylation In Atherosclerosismentioning

confidence: 89%

Section: Histone Methylation In Cvd Progressionmentioning

confidence: 99%

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Yang

Luan

Yuan

et al. 2021

Front. Cardiovasc. Med.

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The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

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“…Histone modification has been shown to regulate factors that are important for trophoblast invasion and migration which is defective in PE [1,46,48]. Recent data of our group showed a decrease of trimethylated lysine 4 of the histone H3 (H3K4me3) and acetylated lysine 9 of the histone H3 (H3K9ac) in EVT cells of placentas of preeclamptic mothers [49]. As H3K4me3 and H3K9ac are known to affect syncytialisation as a necessary precondition for sufficient placentation [50] there might be involvement of histone modification in trophoblast invasion.…”

Section: Introductionmentioning

confidence: 92%

“…A correlation analysis of the IRS of H3K4me3/H3K9ac-published earlier by our group [49] and the expression of PPARγ and RxRα was performed, to outline a possible connection between the transcription modulating PPARγ and RxRα and the histone modifications H3K4me3 and H3K9ac.…”

Section: Correlation Of H3k4me3 and H3k9ac With Pparγ And Rxrαmentioning

confidence: 99%

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

Meister

Hahn

Beyer

et al. 2021

IJMS

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The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.

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Epigenetic modification via H3K4me3 and H3K9ac in human placenta is reduced in preeclampsia

Cited by 12 publications

References 35 publications

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

Sperm Histone H3 Lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

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