Transcriptional mapping and genomic analysis of the cardiac atria and ventricles.

Transcriptional mapping and genomic analysis of the cardiac atria and ventricles.
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DOI:
10.1152/physiolgenomics.00086.2002
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发表时间:
2002-12
影响因子:
4.6
通讯作者:
Xiao-Song Zhao;T. Gallardo;Ling Lin;J. Schageman;R. Shohet
Xiao-Song Zhao;T. Gallardo;Ling Lin;J. Schageman;R. Shohet
中科院分区:
生物学3区
文献类型:
--
作者:
Xiao-Song Zhao;T. Gallardo;Ling Lin;J. Schageman;R. Shohet

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心脏的心房和心室具有不同的发育、结构和生理学。然而,只有少数的基因,这些组织之间的差异是已知的。我们使用小鼠心脏cDNA微阵列来鉴定在心房和心室中差异表达的基因。这些发现的可靠性是支持高度一致的重复杂交,识别以前已知的心房和心室收缩蛋白的亚型,并通过定量PCR和原位杂交的结果确认。我们研究了进化上保守的非编码序列的最差异调节基因,发现心房表达的基因比心室主导基因具有更多的预测肌细胞增强因子2(MEF2)结合位点。我们证实,MEF2家族成员的信息在心房中更丰富,其蛋白质产物也是如此。此外,MEF2活性的转基因报告构建体的活性在心房中响应肥大刺激而优先上调。这项研究提供了一个更好的理解心房和心室之间的分子差异,并建立了一个解剖学上详细评估心脏转录调控的框架。
The atria and ventricles of the heart have distinct development, structure, and physiology. However, only a few of the genes that underlie the differences between these tissues are known. We used a murine cardiac cDNA microarray to identify genes differentially expressed in the atria and ventricles. The reliability of these findings is supported by highly concordant repetition of hybridization, recognition of previously known atrial and ventricular isoforms of contractile proteins, and confirmation of results by quantitative PCR and in situ hybridization. We examined the most differentially regulated genes for evolutionarily conserved noncoding sequences and found that atrial-expressed genes have more predicted myocyte enhancer factor-2 (MEF2) binding sites than ventricle-predominant genes. We confirmed that messages for MEF2 family members are more abundant in the atria, as are their protein products. Moreover, the activity of a transgenic reporter construct for MEF2 activity is preferentially upregulated in the atria in response to hypertrophic stimuli. This study provides a greater understanding of the molecular differences between atria and ventricles and establishes the framework for an anatomically detailed evaluation of cardiac transcriptional regulation.