BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Cloning and characterization of the cardiac-specific Lrrc10 promoter

  • Fan, Xiongwei (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Yang, Qing (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Wang, Youliang (State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Zhang, Yan (State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Wang, Jian (State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Yuan, Jiajia (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Li, Yongqing (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Wang, Yuequn (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Deng, Yun (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Yuan, Wuzhou (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Mo, Xiaoyang (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Wan, Yongqi (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Ocorr, Karen (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University) ;
  • Yang, Xiao (State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology) ;
  • Wu, Xiushan (The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University)
  • Received : 2010.11.12
  • Accepted : 2010.12.17
  • Published : 2011.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Leucine-rich repeat containing protein 10 (LRRC10) is characterized as a cardiac-specific gene, suggesting a role in heart development and disease. A severe cardiac morphogenic defect in zebrafish morphants was recently reported but a contradictory result was found in mice, suggesting a more complicated molecular mechanism exists during mouse embryonic development. To elucidate how LRRC10 is regulated, we analyzed the 5'enhancer region approximately 3 kilo bases (kb) upstream of the Lrrc10 start site using luciferase reporter gene assays. Our characterization of the Lrrc10 promoter indicates it possesses complicated cis-and trans-acting elements. We show that GATA4 and MEF2C could both increase transcriptional activity of Lrrc10 promoter individually but that they do not act synergistically, suggesting that there exists a more complex regulation pattern. Surprisingly, knockout of Gata4 and Mef2c binding sites in the 5’enhancer region (-2,894/-2,889) didn't change the transcriptional activity of the Lrrc10 promoter and the likely GATA4 binding site identified was located in a region only 100 base pair (bp) upstream of the promoter. Our data provides insight into the molecular regulation of Lrrc10 expression, which probably also contributes to its tissue-specific expression.

Keywords

References

  1. Nakane, T., Satoh, T., Inada, Y., Nakayama, J., Itoh, F. and Chiba, S. (2004) Molecular cloning and expression of HRLRRP, a novel heart-restricted leucine-rich repeat protein. Biochem. Biophys. Res. Commun. 314, 1086-1092. https://doi.org/10.1016/j.bbrc.2003.12.202
  2. Adameyko, I. I., Mudry, R. E., Houston-Cummings, N. R., Veselov, A. P., Gregorio, C. C. and Tevosian, S. G. (2005) Expressionand regulation of mouse SERDIN1, a highly conserved cardiac-specific leucine-rich repeat protein. Dev. Dyn. 233, 540-552. https://doi.org/10.1002/dvdy.20368
  3. Kobe, B. and Kajava., A. V. (2001) The leucine-rich repeat as a protein recognition motif. Curr. Opin. Struct. Biol. 11, 725-732. https://doi.org/10.1016/S0959-440X(01)00266-4
  4. Kim, K. H., Kim, T. G., Micales, B. K., Lyons, G. E. and Lee, Y. (2007) Dynamic expression patterns of leucine- rich repeat containing protein 10 in the heart. Dev. Dyn. 236, 2225-2234. https://doi.org/10.1002/dvdy.21225
  5. Kim, K. H., Antkiewicz, D. S., Yan, L., Eliceiri, K. W., Heideman, W., Peterson, R. E. and Lee, Y. (2007) Lrrc10 is required for early heart development and function in zebrafish. Dev. Biol. 308, 494-506. https://doi.org/10.1016/j.ydbio.2007.06.005
  6. Manuylov, N. L., Manuylova, E., Avdoshina, V. and Tevosian, S. (2008) Serdin1/Lrrc10 is Dispensable for Mouse. Development Genesis 46, 441-446. https://doi.org/10.1002/dvg.20422
  7. Molkentin, J. D., Lin, Q., Duncan, S. A. and Olson, E. N. (1997) Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 11, 1061-1072. https://doi.org/10.1101/gad.11.8.1061
  8. Kuo, C. T., Morrisey, E. E., Anandappa, R., Sigrist, K., Lu, M. M., Parmacek, M. S., Soudais, C. and Leiden, J. M. (1997) GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev. 11, 1048-1060. https://doi.org/10.1101/gad.11.8.1048
  9. Lin, Q., Schwarz, J., Bucana, C. and Olson, E. N. (1997) Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276, 1404-1407. https://doi.org/10.1126/science.276.5317.1404
  10. Bi, W., Drake, C. J. and Schwarz, J. J. (1999) The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGF. Dev. Biol. 211, 255-267. https://doi.org/10.1006/dbio.1999.9307
  11. Ko, L, J. and Engel, J, D. (1993) DNA-binding specificities of the GATA transcription factor family. Mol. Cell. Biol. 13, 4011-4022. https://doi.org/10.1128/MCB.13.7.4011
  12. Molkentin, J. D. (2000) The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J. Biol. Chem. 275, 38949-38952. https://doi.org/10.1074/jbc.R000029200
  13. Pikkarainen, S., Tokola, H., Kerkela, R. and Ruskoaho, H. (2004) GATA transcription factors in the developing and adult heart. Cardiovasc. Res. 63, 196-207. https://doi.org/10.1016/j.cardiores.2004.03.025
  14. Black, B. L. and Olson, E. N. (1998) Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins. Annu. Rev. Cell. Dev. Biol. 14, 167-196. https://doi.org/10.1146/annurev.cellbio.14.1.167
  15. Molkentin, J. D. and Olson, E. N. (1996) Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc. Natl. Acad. Sci. 93, 9366-9373. https://doi.org/10.1073/pnas.93.18.9366
  16. Vincentz, J. W., Barnes, R. M., Firulli, B. A., Conway, S. J., and Firulli, A. B. (2008) Cooperative interaction of Nkx2.5 and Mef2c transcription factors during heart development. Dev. Dyn. 237, 3809-3819. https://doi.org/10.1002/dvdy.21803
  17. Ghosh, T. K., Song, F. F., Packham, E. A., Buxton, S., Robinson, T. E., Ronksley, J., Self, T., Bonser, A. J. and Brook, J. D. (2009) Physical interaction between TBX5 and MEF2C Is required for early heart development. Molecular and Cell Biology. 29, 2205-2218. https://doi.org/10.1128/MCB.01923-08
  18. Morin, S., Charron, F., Robitaille, L. and Nemer, M. (2000) GATA-dependent recruitment of MEF2 proteins to target promoters. EMBO 19, 2046-2055. https://doi.org/10.1093/emboj/19.9.2046
  19. Ieda, M., Fu, J. D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G. and Srivastava, D. (2010) Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors. Cell 142, 375-386. https://doi.org/10.1016/j.cell.2010.07.002
  20. Zhu, Y. X. and Li, Y. (2002) Modern molecular biology Beijing Higher Education Press, Beijing, China.
  21. Clark, S. J., Harrison, J. and Molloy, P. L. (1997) Sp1 binding is inhibited by (m)Cp(m)CpG methylation. Gene 195, 67-71. https://doi.org/10.1016/S0378-1119(97)00164-9
  22. Qi, X., Yang, G., Yang, L., Lan, Y., Weng, T., Wang, J., Wu, Z., Xu, J., Gao, X. and Yang, X. (2007) Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development. Dev. Biol. 311, 136-146. https://doi.org/10.1016/j.ydbio.2007.08.022

Cited by

  1. Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4 vol.62, 2013, https://doi.org/10.1016/j.yjmcc.2013.05.020
  2. The Role of Leucine-Rich Repeat Containing Protein 10 (LRRC10) in Dilated Cardiomyopathy vol.7, 2016, https://doi.org/10.3389/fphys.2016.00337
  3. SIVA1 Regulates the Stability of Single-Stranded DNA-Binding Protein 3 Isoforms vol.52, pp.5, 2018, https://doi.org/10.1134/S0026893318050163