This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, C.-Y. Articles by Schwartz, R. J. Search for Related Content PubMed PubMed Citation Articles by Chen, C.-Y. Articles by Schwartz, R. J.

Competition Between Negative Acting YY1 versus Positive Acting Serum Response Factor and Tinman Homologue Nkx-2.5 Regulates Cardiac -Actin Promoter Activity

Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030

Transcription of sarcomeric -actin genes is developmentally regulated during skeletal and cardiac muscle development through fine-tuned control mechanisms involving multiple cooperative and antagonistic transcription factors. Among the cis-acting DNA elements recognized by these factors is the sequence CC(A/T)₆GG of the serum response element (SRE), which is present in a number of growth factor-inducible and myogenic specified genes. We recently showed that the cardiogenic homeodomain factor, Nkx-2.5, served as a positive acting accessory factor for serum response factor (SRF) and together provided strong transcriptional activation of the cardiac -actin promoter. In addition, Nkx-2.5 and SRF collaborated to activate the endogenous murine cardiac -actin gene in 10T1/2 fibroblasts, by a mechanism that involved coassociation of SRF and Nkx-2.5 on intact SREs of the -actin promoter. Here, we show that the second SRE of the avian cardiac -actin promoter served as a binding site for Nkx-2.5, SRF, and zinc finger containing GLI-Krüppel-like factor, YY1. Expression of YY1 inhibited cardiac -actin promoter activity, whereas coexpression of Nkx-2.5 and SRF was able to partially reverse YY1 repression. Displacement of YY1 binding by Nkx-2.5/SRF complex occurs through mutually exclusive binding across the CaSRE2. The interplay and functional antagonism between YY1 and Nkx-2.5/SRF might constitute a developmental as well as a physiologically regulated mechanism that modulates cardiac -actin gene expression during cardiogenesis.

This article has been cited by other articles:

				K. Kawai-Kowase and G. K. Owens Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 2007; 292(1): C59 - C69. [Abstract] [Full Text] [PDF]

				C. C. Sucharov, S. Langer, M. Bristow, and L. Leinwand Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1029 - C1037. [Abstract] [Full Text] [PDF]

				L. Favot, S. M. Hall, S. G. Haworth, and P. R. Kemp Cytoplasmic YY1 Is Associated with Increased Smooth Muscle-Specific Gene Expression: Implications for Neonatal Pulmonary Hypertension Am. J. Pathol., December 1, 2005; 167(6): 1497 - 1509. [Abstract] [Full Text] [PDF]

				C. Rene, M. Taulan, F. Iral, J. Doudement, A. L'Honore, C. Gerbon, J. Demaille, M. Claustres, and M.-C. Romey Binding of serum response factor to cystic fibrosis transmembrane conductance regulator CArG-like elements, as a new potential CFTR transcriptional regulation pathway Nucleic Acids Res., September 16, 2005; 33(16): 5271 - 5290. [Abstract] [Full Text] [PDF]

				S. X. Zhang, E. Garcia-Gras, D. R. Wycuff, S. J. Marriot, N. Kadeer, W. Yu, E. N. Olson, D. J. Garry, M. S. Parmacek, and R. J. Schwartz Identification of Direct Serum-response Factor Gene Targets during Me2SO-induced P19 Cardiac Cell Differentiation J. Biol. Chem., May 13, 2005; 280(19): 19115 - 19126. [Abstract] [Full Text] [PDF]

				K.-H. Lee, S. Evans, T. Y. Ruan, and A. B. Lassar SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer Development, October 1, 2004; 131(19): 4709 - 4723. [Abstract] [Full Text] [PDF]

				C. L. Himeda, J. A. Ranish, J. C. Angello, P. Maire, R. Aebersold, and S. D. Hauschka Quantitative Proteomic Identification of Six4 as the Trex-Binding Factor in the Muscle Creatine Kinase Enhancer Mol. Cell. Biol., March 1, 2004; 24(5): 2132 - 2143. [Abstract] [Full Text] [PDF]

				M. I. Reinhold, D. G. McEwen, and M. C. Naski Fibroblast Growth Factor Receptor 3 Gene: Regulation by Serum Response Factor Mol. Endocrinol., January 1, 2004; 18(1): 241 - 251. [Abstract] [Full Text] [PDF]

				T.-S. Yeh, Y.-M. Lin, R.-H. Hsieh, and M.-J. Tseng Association of Transcription Factor YY1 with the High Molecular Weight Notch Complex Suppresses the Transactivation Activity of Notch J. Biol. Chem., October 24, 2003; 278(43): 41963 - 41969. [Abstract] [Full Text] [PDF]

				C. C. Sucharov, P. Mariner, C. Long, M. Bristow, and L. Leinwand Yin Yang 1 Is Increased in Human Heart Failure and Represses the Activity of the Human {alpha}-Myosin Heavy Chain Promoter J. Biol. Chem., August 15, 2003; 278(33): 31233 - 31239. [Abstract] [Full Text] [PDF]

				S. Konig, J. Burkman, J. Fitzgerald, M. Mitchell, L. Su, and H. Stedman Modular Organization of Phylogenetically Conserved Domains Controlling Developmental Regulation of the Human Skeletal Myosin Heavy Chain Gene Family J. Biol. Chem., July 26, 2002; 277(31): 27593 - 27605. [Abstract] [Full Text] [PDF]

				J. L. Sepulveda, S. Vlahopoulos, D. Iyer, N. Belaguli, and R. J. Schwartz Combinatorial Expression of GATA4, Nkx2-5, and Serum Response Factor Directs Early Cardiac Gene Activity J. Biol. Chem., July 5, 2002; 277(28): 25775 - 25782. [Abstract] [Full Text] [PDF]

				C. P. Mack, M. M. Thompson, S. Lawrenz-Smith, and G. K. Owens Smooth Muscle {alpha}-Actin CArG Elements Coordinate Formation of a Smooth Muscle Cell-Selective, Serum Response Factor-Containing Activation Complex Circ. Res., February 4, 2000; 86(2): 221 - 232. [Abstract] [Full Text] [PDF]

				W. Ding, M. M. Witte, and R. E. Scott Transformation Blocks Differentiation-induced Inhibition of Serum Response Factor Interactions with Serum Response Elements Cancer Res., August 1, 1999; 59(15): 3795 - 3802. [Abstract] [Full Text] [PDF]

				J. A. Spencer, M. L. Major, and R. P. Misra Basic Fibroblast Growth Factor Activates Serum Response Factor Gene Expression by Multiple Distinct Signaling Mechanisms Mol. Cell. Biol., June 1, 1999; 19(6): 3977 - 3988. [Abstract] [Full Text] [PDF]

				J. Ericsson, A. Usheva, and P. A. Edwards YY1 Is a Negative Regulator of Transcription of Three Sterol Regulatory Element-binding Protein-responsive Genes J. Biol. Chem., May 14, 1999; 274(20): 14508 - 14513. [Abstract] [Full Text] [PDF]

				Q. Qian, L. Kuo, Y.-T. Yu, and J. N. Rottman A Concise Promoter Region of the Heart Fatty Acid–Binding Protein Gene Dictates Tissue-Appropriate Expression Circ. Res., February 19, 1999; 84(3): 276 - 289. [Abstract] [Full Text] [PDF]

				F. Galvagni, E. Cartocci, and S. Oliviero The Dystrophin Promoter Is Negatively Regulated by YY1 in Undifferentiated Muscle Cells J. Biol. Chem., December 11, 1998; 273(50): 33708 - 33713. [Abstract] [Full Text] [PDF]

				J. L. Sepulveda, N. Belaguli, V. Nigam, C.-Y. Chen, M. Nemer, and R. J. Schwartz GATA-4 and Nkx-2.5 Coactivate Nkx-2 DNA Binding Targets: Role for Regulating Early Cardiac Gene Expression Mol. Cell. Biol., June 1, 1998; 18(6): 3405 - 3415. [Abstract] [Full Text]

				C. Garat, V. Van Putten, Z. A. Refaat, C. Dessev, S.-Y. Han, and R. A. Nemenoff Induction of Smooth Muscle alpha -Actin in Vascular Smooth Muscle Cells by Arginine Vasopressin Is Mediated by c-Jun Amino-terminal Kinases and p38 Mitogen-activated Protein Kinase J. Biol. Chem., July 14, 2000; 275(29): 22537 - 22543. [Abstract] [Full Text] [PDF]

				C. P. Mack, A. V. Somlyo, M. Hautmann, A. P. Somlyo, and G. K. Owens Smooth Muscle Differentiation Marker Gene Expression Is Regulated by RhoA-mediated Actin Polymerization J. Biol. Chem., January 5, 2001; 276(1): 341 - 347. [Abstract] [Full Text] [PDF]

				J. A. Carson, R. A. Fillmore, R. J. Schwartz, and W. E. Zimmer The Smooth Muscle gamma -Actin Gene Promoter Is a Molecular Target for the Mouse bagpipe Homologue, mNkx3-1, and Serum Response Factor J. Biol. Chem., December 8, 2000; 275(50): 39061 - 39072. [Abstract] [Full Text] [PDF]

				A. Ficzycz, C. Eskiw, D. Meyer, K. E. Marley, M. Hurt, and N. Ovsenek Expression, Activity, and Subcellular Localization of the Yin Yang 1 Transcription Factor in Xenopus Oocytes and Embryos J. Biol. Chem., June 15, 2001; 276(25): 22819 - 22825. [Abstract] [Full Text] [PDF]

				S. S. Bhalla, L. Robitaille, and M. Nemer Cooperative Activation by GATA-4 and YY1 of the Cardiac B-type Natriuretic Peptide Promoter J. Biol. Chem., March 30, 2001; 276(14): 11439 - 11445. [Abstract] [Full Text] [PDF]