Cardiac deletion of Smyd2 is dispensable for mouse heart development.

Cardiac deletion of Smyd2 is dispensable for mouse heart development.
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DOI:
10.1371/journal.pone.0009748
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发表时间:
2010-03-17
期刊:
影响因子:
3.7
通讯作者:
Engel FB
Engel FB
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Diehl F;Brown MA;van Amerongen MJ;Novoyatleva T;Wietelmann A;Harriss J;Ferrazzi F;Böttger T;Harvey RP;Tucker PW;Engel FB

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染色质修饰酶在心脏分化中起关键作用。先前的研究表明,SET和MYND结构域(Smyd)家族的创始成员组蛋白甲基转移酶Smyd1的靶向缺失会干扰心肌细胞的成熟和右心室的正常形成。高度相关的同源物Smyd2是一种在心脏和大脑中表达的组蛋白3赖氨酸4和赖氨酸36特异性甲基转移酶。在这里,我们报道Smyd2在心脏发育过程中差异表达,在新生儿心脏中表达最高。为了阐明Smyd2在心脏中的功能作用,我们产生了Smyd2心肌细胞特异性缺失的条件敲除(cKO)小鼠,并进行了组织学、功能和分子分析。出乎意料的是,Smyd2的心脏缺失对于小鼠心脏的正常形态和功能发育是必不可少的,并且对全局组蛋白3赖氨酸4或36甲基化没有影响。然而,我们为Smyd2在翻译相关基因的转录调控中的潜在作用提供了证据,并揭示Smyd2与Smyd3相似,与RNA聚合酶II以及RNA解旋酶HELZ相互作用。
Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of the histone methyltransferase, Smyd1, the founding member of the SET and MYND domain containing (Smyd) family, interferes with cardiomyocyte maturation and proper formation of the right heart ventricle. The highly related paralogue, Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase expressed in heart and brain. Here, we report that Smyd2 is differentially expressed during cardiac development with highest expression in the neonatal heart. To elucidate the functional role of Smyd2 in the heart, we generated conditional knockout (cKO) mice harboring a cardiomyocyte-specific deletion of Smyd2 and performed histological, functional and molecular analyses. Unexpectedly, cardiac deletion of Smyd2 was dispensable for proper morphological and functional development of the murine heart and had no effect on global histone 3 lysine 4 or 36 methylation. However, we provide evidence for a potential role of Smyd2 in the transcriptional regulation of genes associated with translation and reveal that Smyd2, similar to Smyd3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ.
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