Nishida Wataru, Nakamura Mako, Mori Syunsuke, Takahashi Masanori, Ohkawa Yasuyuki, Tadokoro Satoko, Yoshida Kenji, Hiwada Kunio, Hayashi Ken'ichiro, Sobue Kenji
Department of Neuroscience (D13), Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita City, Osaka 565-0871, Japan.
J Biol Chem. 2002 Mar 1;277(9):7308-17. doi: 10.1074/jbc.M111824200. Epub 2001 Dec 14.
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 alpha(1) 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 alpha(1) 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.
血清反应因子与（CC(A/T)(6)GG）（CArG）盒相互作用以促进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调节因子。α(1)整合素启动子除了CArG盒外还包含两个顺式元件：一个TAAT序列，一个同源结构域蛋白的共有结合位点，以及一个GATA结合盒。作为候选的TAAT结合因子，我们克隆了一个NK家族同源框基因Nkx-3.2，它主要在平滑肌组织和骨骼结构中表达。Nkx-3.2、血清反应因子和GATA-6仅在动脉的中膜平滑肌层中共表达。这三种转录因子与其相应的顺式元件形成复合物，并协同反式激活平滑肌基因，包括α(1)整合素、SM22α和钙调蛋白。NK和GATA家族存在心肌特异性成员，Nkx-2.5、血清反应因子和GATA-4的三联体也反式激活了心钠素基因，该基因包含一个CArG样盒、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，并且GATA和NK家族赋予血清反应因子/CArG相互作用以肌肉特异性。
