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SAP30L(Sin3A 相关蛋白 30 样)参与斑马鱼胚胎心脏发育和造血的调控。

SAP30L (Sin3A-associated protein 30-like) is involved in regulation of cardiac development and hematopoiesis in zebrafish embryos.

机构信息

Paediatric Research Centre, University of Tampere School of Medicine and Tampere University Hospital, 33520 Tampere, Finland.

出版信息

J Cell Biochem. 2012 Dec;113(12):3843-52. doi: 10.1002/jcb.24298.

Abstract

The Sin3A-associated proteins SAP30 and SAP30L share 70% sequence identity and are part of the multiprotein Sin3A corepressor complex. They participate in gene repression events by linking members of the complex and stabilizing interactions among the protein members as well as between proteins and DNA. While most organisms have both SAP30 and SAP30L, the zebrafish is exceptional because it only has SAP30L. Here we demonstrate that SAP30L is expressed ubiquitously in embryonic and adult zebrafish tissues. Knockdown of SAP30L using morpholino-mediated technology resulted in a morphant phenotype manifesting as cardiac insufficiency and defective hemoglobinization of red blood cells. A microarray analysis of gene expression in SAP30L morphant embryos revealed changes in the expression of genes involved in regulation of transcription, TGF-beta signaling, Wnt-family transcription factors, and nuclear genes encoding mitochondrial proteins. The expression of the heart-specific nkx2.5 gene was markedly down-regulated in SAP30L morphants, and the cardiac phenotype could be partially rescued by nkx2.5 mRNA. In addition, changes were detected in the expression of genes known to be important in hemoglobin synthesis and erythropoiesis. Our results demonstrate that SAP30L regulates several transcriptional pathways in zebrafish embryos and is involved in the development of cardiac and hematopoietic systems.

摘要

Sin3A 相关蛋白 SAP30 和 SAP30L 具有 70%的序列同一性,是多蛋白 Sin3A 共抑制复合物的一部分。它们通过连接复合物成员、稳定蛋白成员之间以及蛋白质与 DNA 之间的相互作用,参与基因抑制事件。虽然大多数生物体都有 SAP30 和 SAP30L,但斑马鱼是个例外,因为它只有 SAP30L。在这里,我们证明 SAP30L 在斑马鱼胚胎和成体组织中广泛表达。使用基于 morpholino 的技术敲低 SAP30L 导致形态发生表型,表现为心脏功能不全和红细胞血红蛋白化缺陷。SAP30L 形态发生胚胎基因表达的微阵列分析显示,参与转录调控、TGF-β信号、Wnt 家族转录因子以及编码线粒体蛋白的核基因的基因表达发生变化。SAP30L 形态发生体中心脏特异性 nkx2.5 基因的表达明显下调,nkx2.5 mRNA 可部分挽救心脏表型。此外,还检测到参与血红蛋白合成和红细胞生成的重要基因的表达变化。我们的结果表明,SAP30L 调节斑马鱼胚胎中的几个转录途径,并参与心脏和造血系统的发育。

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