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Activation of skeletal alpha-actin gene transcription: the cooperative formation of serum response factor-binding complexes over positive cis-acting promoter serum response elements displaces a negative-acting nuclear factor enriched in replicating myoblasts and nonmyogenic cells. 总被引:20,自引:10,他引:10
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The atrial natriuretic factor promoter is a downstream target for Nkx-2.5 in the myocardium. 总被引:12,自引:3,他引:9
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D Durocher C Y Chen A Ardati R J Schwartz M Nemer 《Molecular and cellular biology》1996,16(9):4648-4655
The recently described NK2 family of homeodomain proteins are key developmental regulators. In Drosophila melanogaster, two members of this family, bagpipe and tinman, are required for visceral and cardiac mesoderm formation, respectively. In vertebrates, tinman appears to represent a family of closely related NK2 genes, including Nkx-2.5, that are expressed at an early stage in precardiac cells. Consistent with a role for Nkx-2.5 in heart development, inactivation of the Nkx-2.5 gene in mice causes severe cardiac malformations and embryonic lethality. However, little is known about the molecular action of Nkx-2.5 and its targets in cardiac muscle. In this paper, we report the identification and characterization of a functional and highly conserved Nkx-2.5 response element, termed the NKE, in the proximal region of the cardiac atrial natriuretic factor (ANF) promoter. The NKE is composed of two near-consensus NK2 binding sites that are each able to bind purified Nkx-2.5. The NKE is sufficient to confer cardiac cell-specific activity to a minimal TATA-containing promoter and is required for Nkx-2.5 activation of the ANF promoter in heterologous cells. Interestingly, in primary cardiocyte cultures, the NKE contributes to ANF promoter activity in a chamber- and developmental stage-specific manner, suggesting that Nkx-2.5 and/or other related cardiac proteins may play a role in chamber specification. This work provides the identification of a direct target for NK2 homeoproteins in the heart and lays the foundation for further molecular analyses of the role of Nkx-2.5 and other NK2 proteins in cardiac development. 相似文献
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A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes. 总被引:11,自引:0,他引:11
Wataru Nishida Mako Nakamura Syunsuke Mori Masanori Takahashi Yasuyuki Ohkawa Satoko Tadokoro Kenji Yoshida Kunio Hiwada Ken'ichiro Hayashi Kenji Sobue 《The Journal of biological chemistry》2002,277(9):7308-7317
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v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements. 总被引:5,自引:0,他引:5
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K Alexandropoulos S A Qureshi M Rim V P Sukhatme D A Foster 《Nucleic acids research》1992,20(9):2355-2359