Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain.
Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain.
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DOI：
10.1186/s12974-021-02228-6
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发表时间：
2021-08-26
影响因子：
9.3
通讯作者：
Taverna SD
中科院分区：
文献类型：
--
作者：
Stephens KE;Zhou W;Renfro Z;Ji Z;Ji H;Guan Y;Taverna SD
努力了解参与个体对慢性疼痛的易感性的遗传变异性，支持表观遗传机制对上游调控的作用。为了研究存在于外周神经系统中的慢性疼痛的转录组学和表观遗传学基础，我们使用大鼠背根神经节（DRG）的RNA-seq和ATAC-seq来鉴定与两种充分研究的持续性疼痛模型中的疼痛超敏性相关的新分子通路，所述持续性疼痛模型由大鼠坐骨神经的慢性压迫性损伤（CCI）和足底内注射完全弗氏佐剂（CFA）诱导。我们的RNA-seq研究鉴定了与突触组织、膜电位、跨膜转运和离子结合相关的各种生物过程。有趣的是，编码转录调节因子的基因在两种模型中都不成比例地下调。我们的ATAC-seq数据提供了DRG中染色质可及性变化的综合图谱。与原始模型相比，一种或两种模型中共有1123个区域显示出染色质可及性的变化，并且有31个共享差异可及区域（DARs）。DAR的功能注释鉴定了针对每种疼痛模型富集的不同分子功能，这表明在坐骨神经损伤和后爪炎症后，染色质结构可能发生不同的改变。基序分析鉴定了已知在CCI DAR中结合转录因子的17个DNA序列和在CFA DAR中结合转录因子的33个DNA序列。两个图案显着丰富的两种模式。我们对慢性疼痛状态下发生的染色质可及性变化的进一步理解可能会确定在调节DRG基因表达中发挥重要作用的调控基因组元件。在线版本包含补充材料，可通过10.1186/s12974-021-02228-6获得。
Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund’s adjuvant (CFA) in rats. Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. The online version contains supplementary material available at 10.1186/s12974-021-02228-6.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7
作者：
Hammer, Paul;Banck, Michaela S.;Beutler, Andreas S.
通讯作者：
Beutler, Andreas S.
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
影响因子：
3.7
作者：
Dawes JM;Antunes-Martins A;Perkins JR;Paterson KJ;Sisignano M;Schmid R;Rust W;Hildebrandt T;Geisslinger G;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
7.4
作者：
BENNETT, GJ;XIE, YK
通讯作者：
XIE, YK