Neonatal monocytes exhibit a unique histone modification landscape.
Neonatal monocytes exhibit a unique histone modification landscape.
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DOI：
10.1186/s13148-016-0265-7
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发表时间：
2016
影响因子：
5.7
通讯作者：
Schaller MA
中科院分区：
文献类型：
--
作者：
Bermick JR;Lambrecht NJ;denDekker AD;Kunkel SL;Lukacs NW;Hogaboam CM;Schaller MA
新生儿抑制了促炎细胞因子的表达，难以清除病原体。这使得它们特别容易受到感染，但对调节子宫特异性免疫反应的因素知之甚少。表观遗传学，包括组蛋白修饰，可以通过调节染色质结构和稳定性来激活或沉默基因转录，而不影响DNA序列本身，并且是潜在可修饰的。已知组蛋白修饰可调节成人的免疫细胞分化和功能，但尚未在新生儿中进行充分研究。为了阐明组蛋白修饰在新生儿免疫功能中的作用，我们对45例健康新生儿（胎龄23 - 40周）的单核细胞进行了染色质免疫沉淀。随着妊娠接近足月，促炎性IL1B、IL6、IL12B和TNF细胞因子启动子上的活化H3K4me3增加（p <0.01），而抑制性H3K27me3没有变化，这表明早产新生儿中的这些启动子比足月新生儿中的转录因子更不开放和可接近。然后进行染色质免疫沉淀和大规模平行DNA测序（ChIP-seq），以在新生儿和成人CD14+单核细胞中建立H3K4me3、H3K9me3、H3K27me3、H3K4me1、H3K27ac和H3K36me3图谱。随着从新生儿到成人的发育，单核细胞失去了平衡的增强子标记H3K4me1，并获得了激活标记H3K4me3，而没有改变额外的组蛋白修饰。这降低了在免疫学上重要的新生儿单核细胞基因启动子（包括CCR 2、CD300C、ILF2、IL1B和TNF）处的H3K4me3丰度，与基因表达降低相关。这些结果提供了证据，表明新生儿免疫细胞存在于与成人明显不同的表观遗传状态中，并且这种状态有助于机体特异性免疫反应，使它们特别容易受到感染。本文的在线版本（doi：10.1186/s13148 - 016 - 0265 - 7）包含补充材料，可供授权用户使用。
Neonates have dampened expression of pro-inflammatory cytokines and difficulty clearing pathogens. This makes them uniquely susceptible to infections, but the factors regulating neonatal-specific immune responses are poorly understood. Epigenetics, including histone modifications, can activate or silence gene transcription by modulating chromatin structure and stability without affecting the DNA sequence itself and are potentially modifiable. Histone modifications are known to regulate immune cell differentiation and function in adults but have not been well studied in neonates. To elucidate the role of histone modifications in neonatal immune function, we performed chromatin immunoprecipitation on mononuclear cells from 45 healthy neonates (gestational ages 23–40 weeks). As gestation approached term, there was increased activating H3K4me3 on the pro-inflammatory IL1B, IL6, IL12B, and TNF cytokine promoters (p < 0.01) with no change in repressive H3K27me3, suggesting that these promoters in preterm neonates are less open and accessible to transcription factors than in term neonates. Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was then performed to establish the H3K4me3, H3K9me3, H3K27me3, H3K4me1, H3K27ac, and H3K36me3 landscapes in neonatal and adult CD14+ monocytes. As development progressed from neonate to adult, monocytes lost the poised enhancer mark H3K4me1 and gained the activating mark H3K4me3, without a change in additional histone modifications. This decreased H3K4me3 abundance at immunologically important neonatal monocyte gene promoters, including CCR2, CD300C, ILF2, IL1B, and TNF was associated with reduced gene expression. These results provide evidence that neonatal immune cells exist in an epigenetic state that is distinctly different from adults and that this state contributes to neonatal-specific immune responses that leaves them particularly vulnerable to infections. The online version of this article (doi:10.1186/s13148-016-0265-7) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Ross-Innes, Caryn S.;Stark, Rory;Teschendorff, Andrew E.;Holmes, Kelly A.;Ali, H. Raza;Dunning, Mark J.;Brown, Gordon D.;Gojis, Ondrej;Ellis, Ian O.;Green, Andrew R.;Ali, Simak;Chin, Suet-Feung;Palmieri, Carlo;Caldas, Carlos;Carroll, Jason S.
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Chatila, Talal A.
影响因子：
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7
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