Distinct H3K27me3 and H3K27ac Modifications in Neural Tube Defects Induced by Benzo[a]pyrene.
Distinct H3K27me3 and H3K27ac Modifications in Neural Tube Defects Induced by Benzo[a]pyrene.
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苯并[a]芘引起的神经管缺陷中 H3K27me3 和 H3K27ac 的不同修饰
DOI：
10.3390/brainsci13020334
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发表时间：
2023-02-15
期刊：
影响因子：
3.3
通讯作者：
Qiu, Xiu
中科院分区：
文献类型：
--
作者：
Lin, Shanshan;Wang, Chengrui;Li, Zhiwen;Qiu, Xiu
神经管缺陷(NTDS)的病理机制尚不完全清楚。虽然NTDS中组蛋白修饰的失调已经被认识到，但它仍然在全基因组水平上被完全阐明。我们通过切割和标签分析了在E9.5的苯并[a]芘(BaP)诱导的NTDS(250 mg kg−1)的ICR小鼠胚胎的神经组织中H3K27me3和H3K27ac的全基因组占有率。此外，我们还进行了RNA测序(RNA-seq)来研究组蛋白修饰对基因表达的调节。基因本体论和KEGG分析用于预测NTDS的发生途径。我们对BaP-NTD和非BAP-NTD神经组织中组蛋白3赖氨酸27修饰的分析显示，基因组中分别有6045个不同的三甲基化区域和3104个乙酰化区域。功能分析确定了一些独特的丰富BaP-NTD胚胎的途径，包括已知的与神经发育相关的途径，如前/后方模式规范、ewitin受体信号通路、神经元迁移和神经元分化。RNA-seq检测到bap-NTD组和bap-non-NTD组的差异表达基因(Deg)423个。切割-标签和RNA-seq的联合分析发现，在BaP-NTD中，55个DEGS分别被H3K27me3修饰，25个被H3K27ac修饰。在转录调控网络中，转录因子SRSF1、Ume6、Zbtb7b和Cad被预测参与基因表达调控。总之，我们的结果提供了神经管关闭过程中组蛋白修饰的概述，并证明了基因组范围内H3K27me3和H3K27ac的变化在NTDS中与转录谱变化相对应的关键作用。
The pathological mechanisms of neural tube defects (NTDs) are not yet fully understood. Although the dysregulation of histone modification in NTDs is recognized, it remains to be fully elucidated on a genome-wide level. We profiled genome-wide H3K27me3 and H3K27ac occupancy by CUT&Tag in neural tissues from ICR mouse embryos with benzo[a]pyrene (BaP)-induced NTDs (250 mg kg−1) at E9.5. Furthermore, we performed RNA sequencing (RNA-seq) to investigate the regulation of histone modifications on gene expressions. Gene ontology and KEGG analysis were conducted to predict pathways involved in the development of NTDs. Our analysis of histone 3 lysine 27 modification in BaP-NTD neural tissues compared to BaP-nonNTD revealed 6045 differentially trimethylated regions and 3104 acetylated regions throughout the genome, respectively. The functional analysis identified a number of pathways uniquely enriched for BaP-NTD embryos, including known neurodevelopment related pathways such as anterior/posterior pattern specification, ephrin receptor signaling pathway, neuron migration and neuron differentiation. RNA-seq identified 423 differentially expressed genes (DEGs) between BaP-NTD and BaP-nonNTD group. The combination analysis of CUT&Tag and RNA-seq found that 55 DEGs were modified by H3K27me3 and 25 by H3K27ac in BaP-NTD, respectively. In the transcriptional regulatory network, transcriptional factors including Srsf1, Ume6, Zbtb7b, and Cad were predicated to be involved in gene expression regulation. In conclusion, our results provide an overview of histone modifications during neural tube closure and demonstrate a key role of genome-wide alterations in H3K27me3 and H3K27ac in NTDs corresponding with changes in transcription profiles.
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DOI：
10.18632/aging.203524
发表时间：
2021-09-14
期刊：
Aging
影响因子：
--
作者：
Jiang M;Feng J;Fu R;Pan Y;Liu X;Dai J;Jiang C;Hao Y;Ren M
通讯作者：
Ren M
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
16
作者：
Anczuków O;Akerman M;Cléry A;Wu J;Shen C;Shirole NH;Raimer A;Sun S;Jensen MA;Hua Y;Allain FH;Krainer AR
通讯作者：
Krainer AR
影响因子：
82.9
作者：
Greene, NDE;Copp, AJ
通讯作者：
Copp, AJ
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK