Characterrization of cardiac specific specific homebox gene

心脏特异性同源盒基因的表征

• 批准号: 06454288
• 负责人: KOMURO Issei
• 金额: $ 4.8万
• 依托单位: UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454288/
• 关键词: heart; homeobox; atriad natriumctic peptide; transcription; 転写調節; 可変スプライシング; FISH

We have isolated human cardiac specific homeobox-containing gene, CSX.To elucidate the molecular mechanism of cardiac development, we examined upstream and downstream genes of CSX.1. Characterization of upstream genesCSX gene is composed of two exons and one intron. Three isoforms of CSX are derived from one CSX gene by the alternative splicing mechanism. -1 kb promoter sequence of CSX was enough to abundantly express CSX gene in cardiac myocytes and especially 20bp sequences around-110 bp region were important. There were some proteins which bound to these sequences.2. Characterization of downstream genesAmong many genes which are expressed in cardiac myocytes, CSX activated transcription of atrial natriuretic peptide (ANP) and brain creatine kinase genes. There were two CSX binding sites in the promoter of ANP.3. Characterization of associated proteinsSince CSX synergistically activated transcription of ANP gene with a zinc finger protein, GATA4, we examined the protein-protein association between CSX and GATA4. Using GST pull down assay, we elucidated that CSX was associated with GATA4.

为了阐明心脏发育的分子机制，我们研究了CSX.1的上游和下游基因。上游基因特征CSX基因由两个外显子和一个内含子组成。一个CSX基因通过选择性剪接机制产生三种不同的CSX亚型。-1kb的CSX启动子序列足以在心肌细胞中大量表达CSX基因，尤其是-110bP附近的20bP序列更为重要。有一些蛋白质结合在这些序列上。下游基因的特征在心肌细胞表达的众多基因中，CSX激活心钠素(ANP)和脑肌酸激酶基因的转录。在ANP.3的启动子上有两个CSX结合位点。相关蛋白的特征由于CSX协同激活ANP基因的转录与锌指蛋白GATA4，我们研究了CSX和GATA4之间的蛋白质-蛋白质联系。通过GST下调实验，我们阐明了CSX与GATA4相关。

项目成果

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Komuro I、Kudo S 等人：“机械拉伸可激活心肌细胞中应激激活的蛋白质 Kmases。”

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Shiojima I.,Komuro I.et al: "Molecular Cloning and Characterization of Human Cardiac Homeobox Gene CSX1" Circ Res. 79. 920-929 (1996)

Shiojima I.、Komuro I.等人：“人心脏同源框基因 CSX1 的分子克隆和表征”Circ Res。

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Komuro I.，Izumo S.：“心脏病的发育机制”中含有小鼠心脏特异性同源盒的基因”Markwald R.R.，Clark E.B.，Takao A. Futsura N.Y.，679（1995）

塩島一朗,小室一成 他: "Assignment of cardiac homeobox geve CSX to human chromosome 5q 34" GENOMICS. (in press). - (1995)

Ichiro Shioshima、Kazunari Komuro 等人：“心脏同源框 geve CSX 与人类染色体 5q 34 的分配”GENOMICS（正在出版）。