Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis.
Smyd5 plays pivotal roles in both primitive and definitive hematopoiesis during zebrafish embryogenesis.
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DOI：
10.1038/srep29157
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发表时间：
2016-07-05
影响因子：
4.6
通讯作者：
Watanabe S
中科院分区：
文献类型：
--
作者：
Fujii T;Tsunesumi S;Sagara H;Munakata M;Hisaki Y;Sekiya T;Furukawa Y;Sakamoto K;Watanabe S
组蛋白尾部的甲基化在调节广泛的生物过程中起着关键作用。SET和MYND结构域蛋白（SMYD）是一种甲基转移酶，在人类中已鉴定出五个家族成员。已发现SMYD 1、SMYD 2、SMYD 3和SMYD 4在心脏和骨骼肌的致癌和/或发育中起关键作用。然而，SMYD 5的生理功能仍然未知。为了研究Smyd 5在体内的功能，利用斑马鱼作为模型系统。我们首先研究了发育中的斑马鱼胚胎中smart 5的表达模式。Smyd 5转录本在发育早期大量表达，然后逐渐减少。Smyd 5在所有成年组织中均有表达。然后使用Smyd 5吗啉代寡核苷酸（MO）在斑马鱼胚胎中进行Smyd 5的功能丧失分析。注射SmCl 4 5-MO的胚胎显示正常的大体形态发育，包括心脏和骨骼肌。然而，观察到原始和永久造血标记物（包括pu. 1、mpx、l-plastin和cmyb）的表达增加。当我们用CRISPR/Cas9系统在small 5基因中引入突变时，也观察到small 5-MO斑马鱼胚胎的这些表型。由于Smyd 5功能丧失的斑马鱼骨髓标志物的表达升高，我们提出Smyd 5在造血中起着关键作用。
Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system. We first examined smyd5 expression patterns in developing zebrafish embryos. Smyd5 transcripts were abundantly expressed at early developmental stages and then gradually decreased. Smyd5 was expressed in all adult tissues examined. Loss-of-function analysis of Smyd5 was then performed in zebrafish embryos using smyd5 morpholino oligonucleotide (MO). Embryos injected with smyd5-MO showed normal gross morphological development, including of heart and skeletal muscle. However, increased expression of both primitive and definitive hematopoietic markers, including pu.1, mpx, l-plastin, and cmyb, were observed. These phenotypes of smyd5-MO zebrafish embryos were also observed when we introduced mutations in smyd5 gene with the CRISPR/Cas9 system. As the expression of myeloid markers was elevated in smyd5 loss-of-function zebrafish, we propose that Smyd5 plays critical roles in hematopoiesis.