Xiaomin Zhang, Gohar Azhar, Scott Helms, Brian Burton, Chris Huang, Ying Zhong, Xuesong Gu, Hong Fang, Weida Tong, Jeanne Y Wei
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These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well.</p><p><strong>Conclusion and significance: </strong>SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.</p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":" ","pages":"41-59"},"PeriodicalIF":0.0000,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S7457","citationCount":"12","resultStr":"{\"title\":\"Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.\",\"authors\":\"Xiaomin Zhang, Gohar Azhar, Scott Helms, Brian Burton, Chris Huang, Ying Zhong, Xuesong Gu, Hong Fang, Weida Tong, Jeanne Y Wei\",\"doi\":\"10.4137/GRSB.S7457\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg).</p><p><strong>Methodology: </strong>Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. 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引用次数: 12
摘要
背景:为了在体内鉴定血清反应因子(SRF)在基因中的新的心脏结合位点,并研究这些基因对SRF轻度过表达的反应,我们采用了一种具有心脏特异性的转基因小鼠模型,SRF轻度过表达(mild - o SRF Tg)。方法:对6个月大的Mild-O-SRF Tg的心脏进行微阵列实验。我们确定了207个对心脏功能重要的基因,这些基因在体内存在差异表达。其中192个基因的启动子区存在SRF结合基序,即典型的CArG或CArG样(CArG- l)元件。56个具有经典SRF结合位点的基因中有51个以前没有报道过。这些srf调节基因根据其功能分为12类。观察到与心脏能量代谢相关的基因从脂肪酸代谢基因向碳水化合物代谢基因转移。参与转录和离子调控的基因表达减少,但细胞骨架基因的表达显著增加。利用小鼠血流动力学应激模型的公共数据库(GEO数据库),我们还发现在这些心脏缺血或主动脉收缩的心脏中也发生了类似的srf调节基因表达的改变。结论及意义:srf调控基因在多种生理病理条件下均受到积极调控。我们发现大量心脏基因具有经典的SRF结合位点,并且在Mild-O-SRF Tg小鼠心脏中被显著调节。因此,在典型的成人衰老过程中观察到的心脏中SRF蛋白的轻度升高可能对许多SRF调节基因产生重大影响,从而影响心脏的结构和性能。我们的研究结果可以帮助我们加深对SRF调节老年心脏细胞过程的理解。
Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.
Background: To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg).
Methodology: Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well.
Conclusion and significance: SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.