Browsing by Subject "Epigenesis -- genetic"

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    The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish
    (PLOS, 2018-08-15) Xiao, Deyong; Wang, Huijun; Hao, Lili; Guo, Xiao; Ma, Xiaojing; Qian, Yanyan; Chen, Hongbo; Ma, Jing; Zhang, Jin; Sheng, Wei; Shou, Weinian; Huang, Guoying; Ma, Duan; Pediatrics, School of Medicine
    SMYD4 belongs to a family of lysine methyltransferases. We analyzed the role of smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line (smyd4L544Efs*1) using the CRISPR/Cas9 technology. The maternal and zygotic smyd4L544Efs*1 mutants demonstrated severe cardiac malformations, including defects in left-right patterning and looping and hypoplastic ventricles, suggesting that smyd4 was critical for heart development. Importantly, we identified two rare SMYD4 genetic variants in a 208-patient cohort with congenital heart defects. Both biochemical and functional analyses indicated that SMYD4(G345D) was pathogenic. Our data suggested that smyd4 functions as a histone methyltransferase and, by interacting with HDAC1, also serves as a potential modulator for histone acetylation. Transcriptome and bioinformatics analyses of smyd4L544Efs*1 and wild-type developing hearts suggested that smyd4 is a key epigenetic regulator involved in regulating endoplasmic reticulum-mediated protein processing and several important metabolic pathways in developing zebrafish hearts.