Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2004 Nov 16

PMID 15542826

Citations 34

Authors

Tae-Gyun Kim

Junqin Chen

Junich Sadoshima

Youngsook Lee

Affiliations

Soon will be listed here.

Abstract

Mice with a homozygous knockout of the jumonji (jmj) gene showed abnormal heart development and defective regulation of cardiac-specific genes, including the atrial natriuretic factor (ANF). ANF is one of the earliest markers of cardiac differentiation and a hallmark for cardiac hypertrophy. Here, we show that JMJ represses ANF gene expression by inhibiting transcriptional activities of Nkx2.5 and GATA4. JMJ represses the Nkx2.5- or GATA4-dependent activation of the reporter genes containing the ANF promoter-enhancer or containing the Nkx2.5 or GATA4-binding consensus sequence. JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. Using mutational analyses, we mapped the protein-protein interaction domains in JMJ, Nkx2.5, and GATA4. We identified two DNA-binding sites of JMJ in the ANF enhancer by gel mobility shift assays. However, these JMJ-binding sites do not seem to mediate ANF repression by JMJ. Mutational analysis of JMJ indicates that the protein-protein interaction domain of JMJ mediates the repression of ANF gene expression. Therefore, JMJ may play important roles in the down-regulation of ANF gene expression and in heart development.

Citing Articles

Going beyond Polycomb: EZH2 functions in prostate cancer.

Park S, Fong K, Mong E, Martin M, Schiltz G, Yu J Oncogene. 2021; 40(39):5788-5798.

PMID: 34349243 PMC: 8487936. DOI: 10.1038/s41388-021-01982-4.

MicroRNAs in Cardiac Hypertrophy.

Wehbe N, Nasser S, Pintus G, Badran A, Eid A, Baydoun E Int J Mol Sci. 2019; 20(19).

PMID: 31547607 PMC: 6801828. DOI: 10.3390/ijms20194714.

BAOXIN Granules Protected Mouse Model With Elevated Afterload From Cardiac Hypertrophy by Suppressing Both Inflammatory Reaction and Collagen Deposition.

Qiu X, Ma J, Shi Y, Zhang D, Li D, Dong Z Front Physiol. 2019; 10:820.

PMID: 31333486 PMC: 6624790. DOI: 10.3389/fphys.2019.00820.

Myocardial-specific ablation of () leads to dilated cardiomyopathy in mice.

Cho E, Kang H, Kang D, Lee Y J Biol Chem. 2019; 294(13):4981-4996.

PMID: 30700554 PMC: 6442036. DOI: 10.1074/jbc.RA118.005634.

Function of JARID2 in bovines during early embryonic development.

Fu Y, Xu J, Sun X, Jiang H, Han D, Liu C PeerJ. 2018; 5:e4189.

PMID: 29302400 PMC: 5742275. DOI: 10.7717/peerj.4189.

References

Iwahara J, Clubb R . Solution structure of the DNA binding domain from Dead ringer, a sequence-specific AT-rich interaction domain (ARID). EMBO J. 1999; 18(21):6084-94. PMC: 1171673. DOI: 10.1093/emboj/18.21.6084. View

Ordentlich P, Downes M, Evans R . Corepressors and nuclear hormone receptor function. Curr Top Microbiol Immunol. 2001; 254:101-16. DOI: 10.1007/978-3-662-10595-5_5. View

Morin S, Charron F, Robitaille L, Nemer M . GATA-dependent recruitment of MEF2 proteins to target promoters. EMBO J. 2000; 19(9):2046-55. PMC: 305697. DOI: 10.1093/emboj/19.9.2046. View

Lee Y, Song A, Baker R, Micales B, Conway S, Lyons G . Jumonji, a nuclear protein that is necessary for normal heart development. Circ Res. 2000; 86(9):932-8. DOI: 10.1161/01.res.86.9.932. View

Clissold P, Ponting C . JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2beta. Trends Biochem Sci. 2001; 26(1):7-9. DOI: 10.1016/s0968-0004(00)01700-x. View

Dilworth F, Chambon P . Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene. 2001; 20(24):3047-54. DOI: 10.1038/sj.onc.1204329. View

Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R . Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet. 2001; 28(3):276-80. DOI: 10.1038/90123. View

Wang D, Chang P, Wang Z, Sutherland L, Richardson J, Small E . Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 2001; 105(7):851-62. DOI: 10.1016/s0092-8674(01)00404-4. View

Morisco C, Seta K, Hardt S, Lee Y, Vatner S, Sadoshima J . Glycogen synthase kinase 3beta regulates GATA4 in cardiac myocytes. J Biol Chem. 2001; 276(30):28586-97. DOI: 10.1074/jbc.M103166200. View

10.

Bruneau B, Nemer G, Schmitt J, Charron F, Robitaille L, Caron S . A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell. 2001; 106(6):709-21. DOI: 10.1016/s0092-8674(01)00493-7. View

11.

Yamagishi H, Yamagishi C, Nakagawa O, Harvey R, Olson E, Srivastava D . The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol. 2002; 239(2):190-203. DOI: 10.1006/dbio.2001.0417. View

12.

Habets P, Moorman A, Clout D, van Roon M, Lingbeek M, van Lohuizen M . Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. Genes Dev. 2002; 16(10):1234-46. PMC: 186286. DOI: 10.1101/gad.222902. View

13.

Zhang C, McKinsey T, Chang S, Antos C, Hill J, Olson E . Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy. Cell. 2002; 110(4):479-88. PMC: 4459650. DOI: 10.1016/s0092-8674(02)00861-9. View

14.

Chen F, Kook H, Milewski R, Gitler A, Lu M, Li J . Hop is an unusual homeobox gene that modulates cardiac development. Cell. 2002; 110(6):713-23. DOI: 10.1016/s0092-8674(02)00932-7. View

15.

Shin C, Liu Z, Passier R, Zhang C, Wang D, Harris T . Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell. 2002; 110(6):725-35. DOI: 10.1016/s0092-8674(02)00933-9. View

16.

Ganga M, Espinoza H, Cox C, Morton L, Hjalt T, Lee Y . PITX2 isoform-specific regulation of atrial natriuretic factor expression: synergism and repression with Nkx2.5. J Biol Chem. 2003; 278(25):22437-45. DOI: 10.1074/jbc.M210163200. View

17.

Toyoda M, Shirato H, Nakajima K, Kojima M, Takahashi M, Kubota M . jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression. Dev Cell. 2003; 5(1):85-97. DOI: 10.1016/s1534-5807(03)00189-8. View

18.

Kim T, Kraus J, Chen J, Lee Y . JUMONJI, a critical factor for cardiac development, functions as a transcriptional repressor. J Biol Chem. 2003; 278(43):42247-55. DOI: 10.1074/jbc.M307386200. View

19.

NEEDLEMAN P, Adams S, Cole B, Currie M, GELLER D, Michener M . Atriopeptins as cardiac hormones. Hypertension. 1985; 7(4):469-82. DOI: 10.1161/01.hyp.7.4.469. View

20.

Zeller R, Bloch K, Williams B, Arceci R, Seidman C . Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis. Genes Dev. 1987; 1(7):693-8. DOI: 10.1101/gad.1.7.693. View