Apparent microRNA-Target-specific Histone Modification in Mammalian Spermatogenesis

Taguchi, Y-h.

doi:10.4137/ebo.s21832

Cited by 9 publications

(5 citation statements)

References 40 publications

(47 reference statements)

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“…Consistent with our findings, six of our eleven (55%) miRNAs identified in the TBI cohort (let-7a-5p, miR-16-2-5p, -93-5p, -122-5p, -223-3p and -375-3p) were identified in an independent study focused on identifying miRNA with a role in histone modification, including H2A. Only two of our eleven (18%) miRNAs from the WTLI cohort (miR-181a-5p and -200c-3p) were present (47). In addition to DNA damage repair, K48 ubiquitination (GO:0070936) regulates p53 homeostasis (48,49).…”

Section: Discussionmentioning

confidence: 79%

Observation of Unique Circulating miRNA Signatures in Non-Human Primates Exposed to Total-Body vs. Whole Thorax Lung Irradiation

et al. 2021

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A radiological/nuclear (RAD-NUC) incident, especially in an urban setting, results in diverse radiation-induced injuries due to heterogeneities in dose, the extent of partial-body shielding, human biodiversity and pre-existing health conditions. For example, acute radiation syndrome (ARS) can result in death within days to weeks of exposure to 0.7–10 Gy doses and is associated with destruction of the bone marrow, known as hematopoietic ARS (H-ARS). However, partial-body shielding that spares a portion of the bone marrow from exposure can significantly reduce the occurrence of H-ARS, but delayed effects of acute radiation exposure (DEARE) can still occur within months or years after exposure depending on the individual. In a mass casualty event, ideal triage must be able to pre-symptomatically identify individuals likely to develop radiation-induced injuries and provide an appropriate treatment plan. Today, while there are FDA approved treatments for hematopoietic ARS, there are no approved diagnosis for radiation injury and no approved treatments for the broad spectra of injuries associated with radiation. This has resulted in a major capability gap in the nations preparedness to a potentially catastrophic RAD-NUC event. Circulating microRNA (miRNA) are a promising class of biomarkers for this application because the molecules are accessible via a routine blood draw and are excreted by various tissues throughout the body. To test if miRNA can be used to predict distinct tissue-specific radiation-induced injuries, we compared the changes to the circulating miRNA profiles after total-body irradiation (TBI) and whole thorax lung irradiation (WTLI) in non-human primates at doses designed to induce ARS (day 2 postirradiation; 2–6.5 Gy) and DEARE (day 15 postirradiation; 9.8 or 10.7 Gy), respectively. In both models, miRNA sequences were identified that correlated with the onset of severe neutropenia (counts <500 μL–1; TBI) or survival (WTLI). This method identified panels of eleven miRNA for both model and assigned functional roles for the panel members using gene ontology enrichment analysis. A common signature of radiation-induced injury was observed in both models: apoptosis, DNA damage repair, p53 signaling, pro-inflammatory response, and growth factor/cytokine signaling pathways were predicted to be disrupted. In addition, injury-specific pathways were identified. In TBI, pathways associated with ubiquitination, specifically of histone H2A, were enriched, suggesting more impact to DNA damage repair mechanisms and apoptosis. In WTLI, pro-fibrotic pathways including transforming growth factor (TGF-β) and bone morphogenetic protein (BMP) signaling pathways were enriched, consistent with the onset of late lung injury. These results suggest that miRNA may indeed be able to predict the onset of distinct types of radiation-induced injuries.

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Section: Discussionmentioning

confidence: 79%

Observation of Unique Circulating miRNA Signatures in Non-Human Primates Exposed to Total-Body vs. Whole Thorax Lung Irradiation

et al. 2021

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“…Gene expression is influenced by changes in chromatin states through epigenetic mechanisms involving post‐translational modifications of histones (Lindeman et al., ; Ruthenburg, Li, Patel, & Allis, ). While post‐translational modifications of H3K27ac are involved in transcriptional activation (Cao et al., ; Czermin et al., ; Kuzmichev, Nishioka, Erdjument‐Bromage, Tempst, & Reinberg, ; Müller et al., ; Santos & Dean, ; Taguchi, ), those of H3K27me3 result in transcriptional silencing (Lee, ; Santos & Dean, ; Tsai et al., ; Zhao, Sun, Erwin, Song, & Lee, ). Our study is the first to demonstrate the levels of post‐translational changes of H3K27ac vs H3K27me3 in bull spermatozoa.…”

Section: Discussionmentioning

confidence: 99%

Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility

et al. 2017

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Epigenetic modifications in histones are crucial for proper sperm physiology, egg activation and reproductive development of males. The objectives of this study were to determine the conservation and interactomes of histone three (H3) and ascertain the expression dynamics of acetylated and methylated H3 lysine 27 (H3K27ac and H3K27me3) in spermatozoa from Holstein bulls with different fertility. Methods in immunocytochemistry and flow cytometry were used to evaluate the expression dynamics of H3K27ac and H3K27me3 in spermatozoa from 10 bulls with different in vivo fertility. Computational biology methods including Clustal Omega and Cytoscape were performed to determine the evolutionary conservation and interactome of H3. The post-translational modifications (PTM) of H3 (H3K27ac and H3K27me3) had different spatiotemporal dynamics in the sperm head. Intensities of methylation were higher than those of acetylation and inversely correlated between the two fertility groups (p = .0032). The interacting proteins of H3 are involved in critical subcellular processes such as regulation of methylation, nucleosome assembly, regulation of DNA replication and chromatin assembly. These results are significant because they help advance fundamental science and biotechnology of mammalian reproduction.

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“…These above suggested that miRNAs down-regulated in tumor possibly may target epigenetically important genes up-regulated in tumor. Since interaction between epigenetics and miRNAs were recently proposed [44], [45], this observation sounds feasible.…”

Section: Suz12mentioning

confidence: 96%

microRNA-mRNA interaction identification in Wilms tumor using principal component analysis based unsupervised feature extraction

Taguchi

2016

Preprint

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Abstract-Wilms tumor is one of lethal child renal cancers, for which no known disease causing mechanisms exist. In this paper, we tried to identify possible disease causing microRNA(miRNA)-mRNA pairs (interactions) by analyzing (partially matched) miRNA/mRNA gene expression profiles with the recently proposed principal component analysis based unsupervised feature extraction. It successfully identified multiple miRNA-mRNA pairs whose biological natures are convincing. Correlation coefficients between miRNA and mRNA expression in matched parts of profiles turned out to be significantly negative. Constructed miRNA-mRNA network will be a key to understand Wilms tumor causing mechanisms.

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Apparent microRNA-Target-specific Histone Modification in Mammalian Spermatogenesis

Cited by 9 publications

References 40 publications

Observation of Unique Circulating miRNA Signatures in Non-Human Primates Exposed to Total-Body vs. Whole Thorax Lung Irradiation

Observation of Unique Circulating miRNA Signatures in Non-Human Primates Exposed to Total-Body vs. Whole Thorax Lung Irradiation

Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility

microRNA-mRNA interaction identification in Wilms tumor using principal component analysis based unsupervised feature extraction

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