近日，華中農(nóng)業(yè)大學水產(chǎn)學院魚類逆境發(fā)育遺傳學團隊通過研究，發(fā)現(xiàn)了Cu2+通過表觀調(diào)控影響斑馬魚肌原纖維分化機制。相關研究論文以 “Copper ions impair zebrafish skeletal myofibrillogenesis via epigenetic regulation”為題，在線發(fā)表于《The FASEB Journal》。

 

 

　　銅作為一種生物體必需的微量元素，會參與一系列的生理過程，而銅在生物體內(nèi)的穩(wěn)態(tài)失衡也會導致機體發(fā)育異常和疾病發(fā)生。研究銅穩(wěn)態(tài)代謝失衡下的魚類胚胎發(fā)育學對研究魚類環(huán)境脅迫的生物學響應以及適應性進化具有重要意義。該團隊以斑馬魚為模型，發(fā)現(xiàn)Cu2+脅迫可通過抑制Srfa和Myog轉錄活性下調(diào)smyd1b的表達。另外，Cu2+脅迫通過下調(diào)由smyd1b調(diào)控的甲基化組蛋白H3K4me3的表達以及改變smyd5啟動子甲基化水平來抑制斑馬魚肌原纖維的分化。

 

　　碩士研究生靳曉東和博士研究生劉文葉為該論文共同第一作者，劉靜霞教授為該論文的通訊作者。該研究得到了“國家自然科學基金”（32070807）、“藍色糧倉科技創(chuàng)新”重點專項（2018YFD0900101）、中央高校基本科研業(yè)務費華中農(nóng)業(yè)大學交叉專項（2662018JC024）等項目的資助。

 

　　近年來，本團隊圍繞銅穩(wěn)態(tài)代謝失衡下的魚類胚胎發(fā)育學，解析了環(huán)境銅過載或銅轉運基因突變等引起的魚類胚胎細胞中的銅穩(wěn)態(tài)代謝失衡進而導致的神經(jīng)系統(tǒng)、造血系統(tǒng)等發(fā)育缺陷，研究成果已相繼發(fā)表于BBA-GRM，Cell Communication Signaling，F(xiàn)rontiers in Immunology等雜志。

 

　　【英文摘要】

 

　　Unbalanced copper （Cu2+） homeostasis is associated with the developmental defects of vertebrate myogenesis, but the underlying molecular mechanisms remain elusive. In this study, it was found that Cu2+ stressed zebrafish embryos and larvae showed reduced locomotor speed as well as loose and decreased myofibrils in skeletal muscle, coupled with the downregulated expression of muscle fiber markers mylpfa and smyhc1l and the irregular arrangement of myofibril and sarcomere. Meanwhile, the Cu2+ stressed zebrafish embryos and larvae also showed significant reduction in the expression of H3K4 methyltransferase smyd1b transcripts and H3K4me3 protein as well as in the binding enrichment of H3K4me3 on gene mylpfa promoter in skeletal muscle cells, suggesting that smyd1b—H3K4me3 axis mediates the Cu2+-induced myofibrils specification defects. Additionally, whole genome DNA methylation sequencing unveiled that the gene smyd5 exhibited significant promoter hyper-methylation and increased expression in Cu2+ stressed embryos, and the ectopic expression of smyd5 in zebrafish embryos also induced the myofibrils specification defects as those observed in Cu2+ stressed embryos. Moreover, Cu2+ was shown to suppress myofibrils specification and smyd1b promoter transcriptional activity directly independent of the integral function of copper transporter cox17 and atp7b. All these data may shed light on the linkage of unbalanced copper homeostasis with specific gene promoter methylation and epigenetic histone protein modification as well as the resultant signaling transduction and the myofibrillogenesis defects.

 

　　論文鏈接：https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202100183R