A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes
A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes
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DOI：
10.1074/jbc.m111824200
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Sobue, K
中科院分区：
文献类型：
--
作者：
Nishida, W;Nakamura, M;Sobue, K
血清反应因子和(CC(A/T)(6)GG)(Carg)box相互作用，促进c-fos和肌肉基因的转录；这种组织特异性活性可能需要血清反应因子的共同调节。α整合素启动子除了Carg盒外，还含有两个顺式元件：Taat序列、同源蛋白的共同结合部位和GATA结合盒。作为候选Taat结合因子，我们克隆了NK家族同源异型盒基因Nkx-3.2，该基因主要在平滑肌组织和骨骼结构中表达。血清反应因子NKX-3.2和GATA-6仅在动脉中膜平滑肌层共表达。这三个转录因子与其相应的顺式元件形成一个复合体，并协同反式激活平滑肌基因，包括a、整合素、SM22pha和钙调蛋白。心肌特异的NK和GATA家族成员存在，Nkx-2.5、血清反应因子和GATA-4三联体也反式激活了心房利钠因子基因，该基因包含一个Carg样框、一个GATA结合盒和一个NK结合元件。我们的研究结果表明，平滑肌和心肌具有共同的转录机制，GATA和NK家族在血清反应因子/Carg相互作用中具有肌肉特异性。
Serum response factor and the (CC(A/T)(6)GG) (CArG) box interact to promote the transcription of c-fos and muscle genes; this tissue-specific activity may require co-regulators for serum response factor. The a, integrin promoter contains two cis-elements besides the CArG box: a TAAT sequence, a consensus binding site for homeoproteins, and a GATA-binding box. As a candidate TAAT-binding factor, we cloned an NK family homeobox gene, Nkx-3.2, which is expressed mainly in smooth muscle tissues and skeletal structures. Nkx-3.2, serum response factor, and GATA-6 were co-expressed only in the medial smooth muscle layer of arteries. These three transcription factors formed a complex with their corresponding cis-elements and cooperatively transactivated smooth muscle genes, including a, integrin, SM22alpha, and caldesmon. Cardiac muscle-specific members of the NK and GATA families exist, and the triad of Nkx-2.5, serum response factor, and GATA-4 also transactivated the cardiac atrial natriuretic factor gene, which contains a CArG-like box, a GATA-binding box, and an NK-binding element. Our findings demonstrate that smooth and cardiac muscle have a shared transcriptional machinery and that the GATA and NK families confer muscle specificity on the serum response factor/CArG interaction.