Laboratory of Evolutionary and Adaptive Physiology, Institute of Life, Earth and Environment, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium; Coastal Ecology Section, Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Wadden Sea Station Sylt, List, Germany.
Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Box 870344, Tuscaloosa, AL 35487, USA.
Gene. 2019 Mar 1;687:173-187. doi: 10.1016/j.gene.2018.11.046. Epub 2018 Nov 17.
Histone modifications such as methylation of key lysine residues play an important role in embryonic development in a variety of organisms such as of Pacific oysters, zebrafish and mice. The action of demethylase ("erasers") and methyltransferase ("writers") enzymes regulates precisely the methylation status of each lysine residue. However, despite fishes being very useful model organisms in medicine, evolution and ecotoxicology, most studies have focused on mammalian and plant model organisms, and mechanisms underlying regulation of histones are unknown in fish development outside of zebrafish. Here, putative histone lysine demethylases (Kdm) and methyltransferases (Kmt) were identified in an isogenic lineage of the self-fertilizing hermaphroditic vertebrate, the mangrove rivulus fish, Kryptolebias marmoratus. Evolutionary relationships with other animal demethylases and methyltransferases were examined, and expression patterns during embryonic development and in adult tissues were characterized. Twenty-five Kdm orthologues (Jarid2, Jmjd1c, Jmjd4, Jmjd6, Jmjd7, Jmjd8, Kdm1a, Kdm1b, Kdm2a, Kdm2b, Kdm3b, Kdm4a, Kdm4b, Kdm4c, Kdm5a, Kdm5b, Kdm5c, Kdm6a, Kdm6b, Kdm7a, Kdm8, Kdm9, UTY, Phf2 and Phf8) and forty-eight Kmt orthologues (Ezh1, Ezh2, Setd2, Nsd1, Nsd2, Nsd3, Ash1l, Kmt2e, Setd5, Prdm1, Prdm2, Prdm4, Prdm5, Prdm6, Prdm8, Prdm9, Prdm10, Prdm11, Prdm12, Prdm13, Prdm14, Prdm15, Prdm16, Setd3, Setd4, Setd6, Setd1a, Setd1b, Kmt2a, Kmt2b, Kmt2c, Kmt2d, Kmt5a, Kmt5b, Ehmt1, Ehmt2, Suv39h1, Setmar, Setdb1, Setdb2, Smyd1, Smyd2, Smyd3, Smyd4, Smyd5, Setd7, Setd9, Dot1l) were discovered. Expression patterns of both Kdm and Kmt were variable during embryonic development with a peak in gastrula stage and a reduction in later embryogenesis. Expression of both Kdm and Kmt was higher in male brains compared to hermaphrodite brains whereas specific expression patterns of Kdm and Kmt were observed in the hermaphrodite ovotestes and male testes, respectively. Putative histone demethylases (Kdm) and methyltransferases (Kmt) were for the first time characterized in a teleost besides zebrafish, the mangrove rivulus. Their domain conservation and expression profiles suggest that they might play important roles during development, gametogenesis and neurogenesis, which raises questions about epigenetic regulation of these processes by histone lysine methylation in K. marmoratus. Due to its peculiar mode of reproduction and the natural occurrence of isogenic lineages, this new model species is of great interest for understanding epigenetic contributions to the regulation of development and reproduction.
组蛋白修饰，如关键赖氨酸残基的甲基化，在各种生物体的胚胎发育中起着重要作用，如太平洋牡蛎、斑马鱼和小鼠。去甲基酶（“橡皮擦”）和甲基转移酶（“书写器”）酶的作用精确调节每个赖氨酸残基的甲基化状态。然而，尽管鱼类作为医学、进化和生态毒理学非常有用的模式生物，但大多数研究都集中在哺乳动物和植物模式生物上，鱼类除了斑马鱼以外的发育过程中组蛋白调节的机制尚不清楚。在这里，在自交雌雄同体的红树林洄游鱼（Kryptolebias marmoratus）的同系物中，鉴定出了假定的组蛋白赖氨酸去甲基酶（Kdm）和甲基转移酶（Kmt）。与其他动物去甲基酶和甲基转移酶的进化关系进行了研究，并对胚胎发育过程中的表达模式和成年组织中的表达模式进行了表征。鉴定出了 25 个 Kdm 同源物（Jarid2、Jmjd1c、Jmjd4、Jmjd6、Jmjd7、Jmjd8、Kdm1a、Kdm1b、Kdm2a、Kdm2b、Kdm3b、Kdm4a、Kdm4b、Kdm4c、Kdm5a、Kdm5b、Kdm5c、Kdm6a、Kdm6b、Kdm7a、Kdm8、Kdm9、UTY、Phf2 和 Phf8）和 48 个 Kmt 同源物（Ezh1、Ezh2、Setd2、Nsd1、Nsd2、Nsd3、Ash1l、Kmt2e、Setd5、Prdm1、Prdm2、Prdm4、Prdm5、Prdm6、Prdm8、Prdm9、Prdm10、Prdm11、Prdm12、Prdm13、Prdm14、Prdm15、Prdm16、Setd3、Setd4、Setd6、Setd1a、Setd1b、Kmt2a、Kmt2b、Kmt2c、Kmt2d、Kmt5a、Kmt5b、Ehmt1、Ehmt2、Suv39h1、Setmar、Setdb1、Setdb2、Smyd1、Smyd2、Smyd3、Smyd4、Smyd5、Setd7、Setd9、Dot1l）。在胚胎发育过程中，Kdm 和 Kmt 的表达模式具有变异性，在原肠胚期达到峰值，随后在胚胎发生后期减少。与雌雄同体大脑相比，雄性大脑中的 Kdm 和 Kmt 表达更高，而 Kdm 和 Kmt 的特定表达模式分别在雌雄同体的卵睾和雄性睾丸中观察到。首次在除斑马鱼以外的硬骨鱼中对组蛋白去甲基酶（Kdm）和甲基转移酶（Kmt）进行了描述。它们的结构域保守性和表达谱表明，它们可能在发育、配子发生和神经发生过程中发挥重要作用，这引发了关于 K. marmoratus 中组蛋白赖氨酸甲基化对这些过程的表观遗传调控的问题。由于其独特的繁殖方式和同系物的自然发生，这种新的模式物种对于理解表观遗传对发育和繁殖的调节作用非常有兴趣。
