The H3K27 demethylase controls the lateral line embryogenesis of zebrafish.
The H3K27 demethylase controls the lateral line embryogenesis of zebrafish.
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H3K27 去甲基化酶控制斑马鱼的侧线胚胎发生
DOI：
10.1007/s10565-021-09669-y
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发表时间：
2023-06
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
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作者：
Kdm 6 b是一种特异性的组蛋白3赖氨酸27（H3 K27）去甲基化酶，参与细胞分化、细胞命运决定和多器官发生等多种发育过程。本研究通过调控kdm 6 bb基因的转录水平来研究其在控制斑马鱼听觉器官发育中的潜在作用。采用吗啉代反义寡核苷酸（morpholino antisense oligonucleotide，MO）诱导Kdm 6 b缺陷，免疫组化和原位杂交分析Kdm 6 b缺陷的形态学改变和胚胎机制。Kdm 6 bb在斑马鱼胚胎发育早期的原基和神经乳头中表达，提示Kdm 6 b在机械感觉器官的发育中具有潜在的功能。敲低kdm 6 bb基因可严重影响后侧线原基细胞的迁移和增殖，减少神经瘤沿着的数量，mRNA介导的拯救试验可部分更新神经瘤。kdm 6 bb的丢失可能与迁移原基中趋化因子基因cxcl 12 a和cxcr 4 b/cxcr 7 b的异常表达有关。抑制kdm 6 bb可降低Fgf信号通路中相关基因的表达，而增加Wnt/β-catenin信号通路中axin 2和lef 1的表达水平。总之，我们的研究结果表明，Kdm 6 b通过介导趋化因子基因表达和Wnt、Fgf信号通路，在引导原基迁移和调节神经瘤沉积中发挥重要作用。由于组蛋白甲基化和去甲基化是可逆的，靶向Kdm 6 b可能成为治疗听力障碍的新方案。在线版本包含补充材料，可通过10.1007/s10565-021-09669-y获得。
Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/β-catenin signaling during the migrating stage. Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders. The online version contains supplementary material available at 10.1007/s10565-021-09669-y.
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抑制 H3K27me3 组蛋白去甲基化酶活性可阻止斑马鱼侧线神经丘的增殖再生
影响因子：
4.8
作者：
Bao B;He Y;Tang D;Li W;Li H
通讯作者：
Li H
影响因子：
17.1
作者：
Bayliss J;Mukherjee P;Lu C;Jain SU;Chung C;Martinez D;Sabari B;Margol AS;Panwalkar P;Parolia A;Pekmezci M;McEachin RC;Cieslik M;Tamrazi B;Garcia BA;La Rocca G;Santi M;Lewis PW;Hawkins C;Melnick A;David Allis C;Thompson CB;Chinnaiyan AM;Judkins AR;Venneti S
通讯作者：
Venneti S
影响因子：
10.5
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
3.5
作者：
Fellous, Alexandre;Earley, Ryan L.;Silvestre, Frederic
通讯作者：
Silvestre, Frederic
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian