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. 1997 Jul 1;325(Pt 1):47–51. doi: 10.1042/bj3250047

A conserved GATA motif in a tissue-specific DNase I hypersensitive site of the cardiac alpha-myosin heavy chain gene.

W Y Huang 1, C C Liew 1
PMCID: PMC1218527  PMID: 9224628

Abstract

Transgenic analysis has indicated that far upstream regulatory elements of the cardiac alpha-myosin heavy chain (MyHC) gene are required for appropriate transgene expression [Subramaniam, Gulick, Neumann, Knotts and Robbins (1993) J. Biol. Chem. 268, 4331-4336]. In an attempt to identify these as-yet-undefined regulatory elements, we mapped the DNase I hypersensitive sites (DHSs) in the 4 kb upstream region of the hamster cardiac alpha-MyHC gene. When using nuclei isolated from late-gestational and adult heart ventricles, a strong DHS was identified in the -1.9 kb region (alpha-1.9 kb site). It cannot be detected in kidney, liver or cardiofibroblast nuclei. Within this site, we found a conserved GATA-motif that interacts specifically with GATA-binding factors in nuclear extracts of cardiomyocytes at various developmental stages. These data provide further evidence to support the role of GATA factors in the regulation of cardiac alpha-MyHC gene expression.

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Selected References

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  1. Adolph E. A., Subramaniam A., Cserjesi P., Olson E. N., Robbins J. Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene. J Biol Chem. 1993 Mar 15;268(8):5349–5352. [PubMed] [Google Scholar]
  2. Andrews N. C., Faller D. V. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991 May 11;19(9):2499–2499. doi: 10.1093/nar/19.9.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arceci R. J., King A. A., Simon M. C., Orkin S. H., Wilson D. B. Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart. Mol Cell Biol. 1993 Apr;13(4):2235–2246. doi: 10.1128/mcb.13.4.2235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elgin S. C. The formation and function of DNase I hypersensitive sites in the process of gene activation. J Biol Chem. 1988 Dec 25;263(36):19259–19262. [PubMed] [Google Scholar]
  5. Feo S., Antona V., Barbieri G., Passantino R., Calì L., Giallongo A. Transcription of the human beta enolase gene (ENO-3) is regulated by an intronic muscle-specific enhancer that binds myocyte-specific enhancer factor 2 proteins and ubiquitous G-rich-box binding factors. Mol Cell Biol. 1995 Nov;15(11):5991–6002. doi: 10.1128/mcb.15.11.5991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Flink I. L., Morkin E. Interaction of thyroid hormone receptors with strong and weak cis-acting elements in the human alpha-myosin heavy chain gene promoter. J Biol Chem. 1990 Jul 5;265(19):11233–11237. [PubMed] [Google Scholar]
  7. Grépin C., Dagnino L., Robitaille L., Haberstroh L., Antakly T., Nemer M. A hormone-encoding gene identifies a pathway for cardiac but not skeletal muscle gene transcription. Mol Cell Biol. 1994 May;14(5):3115–3129. doi: 10.1128/mcb.14.5.3115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gustafson T. A., Bahl J. J., Markham B. E., Roeske W. R., Morkin E. Hormonal regulation of myosin heavy chain and alpha-actin gene expression in cultured fetal rat heart myocytes. J Biol Chem. 1987 Sep 25;262(27):13316–13322. [PubMed] [Google Scholar]
  9. Heikinheimo M., Scandrett J. M., Wilson D. B. Localization of transcription factor GATA-4 to regions of the mouse embryo involved in cardiac development. Dev Biol. 1994 Aug;164(2):361–373. doi: 10.1006/dbio.1994.1206. [DOI] [PubMed] [Google Scholar]
  10. Huang W. Y., Cukerman E., Liew C. C. Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-encoding gene and isolation of a human GATA-4 cDNA. Gene. 1995 Apr 3;155(2):219–223. doi: 10.1016/0378-1119(94)00893-w. [DOI] [PubMed] [Google Scholar]
  11. Ip H. S., Wilson D. B., Heikinheimo M., Tang Z., Ting C. N., Simon M. C., Leiden J. M., Parmacek M. S. The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells. Mol Cell Biol. 1994 Nov;14(11):7517–7526. doi: 10.1128/mcb.14.11.7517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jackowski G., Liew C. C. Fractionation of rat ventricular nuclei. Biochem J. 1980 May 15;188(2):363–373. doi: 10.1042/bj1880363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jaynes J. B., Johnson J. E., Buskin J. N., Gartside C. L., Hauschka S. D. The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer. Mol Cell Biol. 1988 Jan;8(1):62–70. doi: 10.1128/mcb.8.1.62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laverriere A. C., MacNeill C., Mueller C., Poelmann R. E., Burch J. B., Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994 Sep 16;269(37):23177–23184. [PubMed] [Google Scholar]
  15. Lee M. E., Temizer D. H., Clifford J. A., Quertermous T. Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells. J Biol Chem. 1991 Aug 25;266(24):16188–16192. [PubMed] [Google Scholar]
  16. Lompré A. M., Nadal-Ginard B., Mahdavi V. Expression of the cardiac ventricular alpha- and beta-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem. 1984 May 25;259(10):6437–6446. [PubMed] [Google Scholar]
  17. Lyons G. E., Schiaffino S., Sassoon D., Barton P., Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990 Dec;111(6 Pt 1):2427–2436. doi: 10.1083/jcb.111.6.2427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mably J. D., Sole M. J., Liew C. C. Characterization of the GArC motif. A novel cis-acting element of the human cardiac myosin heavy chain genes. J Biol Chem. 1993 Jan 5;268(1):476–482. [PubMed] [Google Scholar]
  19. Molkentin J. D., Brogan R. S., Jobe S. M., Markham B. E. Expression of the alpha-myosin heavy chain gene in the heart is regulated in part by an E-box-dependent mechanism. J Biol Chem. 1993 Feb 5;268(4):2602–2609. [PubMed] [Google Scholar]
  20. Molkentin J. D., Kalvakolanu D. V., Markham B. E. Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene. Mol Cell Biol. 1994 Jul;14(7):4947–4957. doi: 10.1128/mcb.14.7.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Molkentin J. D., Markham B. E. An M-CAT binding factor and an RSRF-related A-rich binding factor positively regulate expression of the alpha-cardiac myosin heavy-chain gene in vivo. Mol Cell Biol. 1994 Aug;14(8):5056–5065. doi: 10.1128/mcb.14.8.5056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Molkentin J. D., Markham B. E. Myocyte-specific enhancer-binding factor (MEF-2) regulates alpha-cardiac myosin heavy chain gene expression in vitro and in vivo. J Biol Chem. 1993 Sep 15;268(26):19512–19520. [PubMed] [Google Scholar]
  23. Pevny L., Simon M. C., Robertson E., Klein W. H., Tsai S. F., D'Agati V., Orkin S. H., Costantini F. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature. 1991 Jan 17;349(6306):257–260. doi: 10.1038/349257a0. [DOI] [PubMed] [Google Scholar]
  24. Subramaniam A., Gulick J., Neumann J., Knotts S., Robbins J. Transgenic analysis of the thyroid-responsive elements in the alpha-cardiac myosin heavy chain gene promoter. J Biol Chem. 1993 Feb 25;268(6):4331–4336. [PubMed] [Google Scholar]
  25. Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
  26. Wall L., deBoer E., Grosveld F. The human beta-globin gene 3' enhancer contains multiple binding sites for an erythroid-specific protein. Genes Dev. 1988 Sep;2(9):1089–1100. doi: 10.1101/gad.2.9.1089. [DOI] [PubMed] [Google Scholar]
  27. Wang D. L., Chen J. J., Shin N. L., Kao Y. C., Hsu K. H., Huang W. Y., Liew C. C. Endothelin stimulates cardiac alpha- and beta- myosin heavy chain gene expression. Biochem Biophys Res Commun. 1992 Mar 31;183(3):1260–1265. doi: 10.1016/s0006-291x(05)80326-2. [DOI] [PubMed] [Google Scholar]
  28. Wang R., Sole M. J., Cai X., Liew C. C. Characterization and structural organization of the cardiac beta-myosin heavy chain gene from Syrian hamster. J Mol Cell Cardiol. 1995 Apr;27(4):1075–1087. doi: 10.1016/0022-2828(95)90076-4. [DOI] [PubMed] [Google Scholar]
  29. Wang R., Sole M. J., Cukerman E., Liew C. C. Characterization and nucleotide sequence of the cardiac alpha-myosin heavy chain gene from Syrian hamster. J Mol Cell Cardiol. 1994 Sep;26(9):1155–1165. doi: 10.1006/jmcc.1994.1134. [DOI] [PubMed] [Google Scholar]
  30. Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]

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