Perinatal inflammation alters histone 3 and histone 4 methylation patterns: Effects of MiR-29b supplementation.
Perinatal inflammation alters histone 3 and histone 4 methylation patterns: Effects of MiR-29b supplementation.
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DOI：
10.1016/j.redox.2020.101783
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发表时间：
2021-01
期刊：
影响因子：
11.4
通讯作者：
Rogers LK
中科院分区：
文献类型：
--
作者：
Sugar SS;Heyob KM;Cheng X;Lee RJ;Rogers LK
早产仍然是一个主要的健康问题，产妇炎症已被证明发挥作用。母体炎症和新生儿高氧的结合有助于影响基因表达和支气管肺发育不良（BPD）发展的表观遗传变化。我们之前已经证明了在患有严重BPD的婴儿中以及在我们的母体炎症和新生儿高氧暴露的小鼠模型中miR-29 b的抑制和DNA甲基化的增加。本研究进一步探讨了小鼠模型中的表观遗传变化，包括组蛋白甲基化。我们确定了暴露小鼠组蛋白甲基化的整体抑制，并验证了明确定义的组蛋白修饰的表达减少，特别是H3 K4 me 3，H3 K27 me 3，H3 K36 me 2，H3 K79 me 2和H4 K20 me 3。我们进一步验证了恢复miR-29 b表达将恢复组蛋白甲基化标记的假设。使用miR-29 b的脂质纳米颗粒递送，重新建立了H3 K4 me 3、H3 K27 me 3和H4 K20 me 3的部分至完全甲基化;所有三甲基化标记。为了确定暴露小鼠甲基化降低的原因，我们测量了常见的甲基化酶和去甲基化酶。我们发现SUV 40 H2的表达减少，这是一种主要与H4 K20 me 3相关的甲基化酶。需要进一步的研究来确定全球组蛋白甲基化减少的原因和潜在的治疗机会。在暴露于围产期炎症的小鼠中，整体组蛋白甲基化降低。脂质纳米颗粒递送miR-29 b部分地将三甲基化恢复至对照水平。改变的组蛋白甲基化可能参与肺泡化缺陷。
Preterm birth is still a major health problem and maternal inflammation has been shown to play a role. The combination of maternal inflammation and neonatal hyperoxia contributes to epigenetic changes that influence gene expression and the development of bronchopulmonary dysplasia (BPD). We have previously demonstrated suppression of miR-29b and increases in DNA methylation in infants with severe BPD and in our mouse model of maternal inflammation and neonatal hyperoxia exposure. The present studies further explored epigenetic changes in the murine model to include histone methylation. We identified a global suppression of histone methylation in exposed mice and validated decreases in expression in well-defined histone modifications, specifically H3K4me3, H3K27me3, H3K36me2, H3K79me2, and H4K20me3. We further tested the hypothesis that restoration of miR-29b expression would restore the histone methylation marks. Using lipid nanoparticle delivery of miR-29b, partial to full methylation was reestablished for H3K4me3, H3K27me3, and H4K20me3; all tri-methylation marks. To identify the causes of decreased methylation in exposed mice, we measured commonly identified methylases and demethylases. We found a decreased expression of SUV40H2, a methylase primarily associated with H4K20me3. Further studies are needed to identify the causes for the decreased global histone methylation and potential therapeutic opportunities. Global histone methylation is decreased in mice exposed to perinatal inflammation. Lipid nano-particle delivery of miR-29b partially restored tri-methylation to control levels. Altered histone methylation may be involved in alveolarization deficits.
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影响因子：
14.9
作者：
Girardot M;Hirasawa R;Kacem S;Fritsch L;Pontis J;Kota SK;Filipponi D;Fabbrizio E;Sardet C;Lohmann F;Kadam S;Ait-Si-Ali S;Feil R
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DOI：
10.1165/rcmb.2010-0323oc
发表时间：
2011-08-01
影响因子：
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DOI：
10.1152/ajplung.00390.2016
发表时间：
2016-11-01
影响因子：
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影响因子：
3.5
作者：
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影响因子：
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作者：
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