2rq5

Structural highlights

Function

[JARD2_MOUSE] Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis. Acts by modulating histone methyltransferase activity and promoting the recruitment of histone methyltransferase complexes to their target genes. Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells. Does not have histone demethylase activity but regulates activity of various histone methyltransferase complexes. In embryonic stem cells, it associates with the PRC2 complex and inhibits trimethylation of 'Lys-27' of histone H3 (H3K27me3) by the PRC2 complex, thereby playing a key role in differentiation of embryonic stem cells and normal development. In cardiac cells, it is required to repress expression of cyclin-D1 (CCND1) by activating methylation of 'Lys-9' of histone H3 (H3K9me) by the GLP1/EHMT1 and G9a/EHMT2 histone methyltransferases. Also acts as a transcriptional repressor of ANF via its interaction with GATA4 and NKX2-5. Participates in the negative regulation of cell proliferation signaling.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Toyoda M, Kojima M, Takeuchi T. Jumonji is a nuclear protein that participates in the negative regulation of cell growth. Biochem Biophys Res Commun. 2000 Aug 2;274(2):332-6. PMID:10913339 doi:http://dx.doi.org/10.1006/bbrc.2000.3138
2. ↑ Lee Y, Song AJ, Baker R, Micales B, Conway SJ, Lyons GE. Jumonji, a nuclear protein that is necessary for normal heart development. Circ Res. 2000 May 12;86(9):932-8. PMID:10807864
3. ↑ Toyoda M, Shirato H, Nakajima K, Kojima M, Takahashi M, Kubota M, Suzuki-Migishima R, Motegi Y, Yokoyama M, Takeuchi T. jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression. Dev Cell. 2003 Jul;5(1):85-97. PMID:12852854
4. ↑ Kim TG, Kraus JC, Chen J, Lee Y. JUMONJI, a critical factor for cardiac development, functions as a transcriptional repressor. J Biol Chem. 2003 Oct 24;278(43):42247-55. Epub 2003 Jul 30. PMID:12890668 doi:http://dx.doi.org/10.1074/jbc.M307386200
5. ↑ Kim TG, Chen J, Sadoshima J, Lee Y. Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. Mol Cell Biol. 2004 Dec;24(23):10151-60. PMID:15542826 doi:http://dx.doi.org/10.1128/MCB.24.23.10151-10160.2004
6. ↑ Jung J, Kim TG, Lyons GE, Kim HR, Lee Y. Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. J Biol Chem. 2005 Sep 2;280(35):30916-23. Epub 2005 May 3. PMID:15870077 doi:http://dx.doi.org/10.1074/jbc.M414482200
7. ↑ Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH. Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2009 Dec 24;139(7):1303-14. PMID:20064376 doi:http://dx.doi.org/S0092-8674(09)01507-4
8. ↑ Peng JC, Valouev A, Swigut T, Zhang J, Zhao Y, Sidow A, Wysocka J. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell. 2009 Dec 24;139(7):1290-302. doi: 10.1016/j.cell.2009.12.002. PMID:20064375 doi:http://dx.doi.org/10.1016/j.cell.2009.12.002
9. ↑ Shirato H, Ogawa S, Nakajima K, Inagawa M, Kojima M, Tachibana M, Shinkai Y, Takeuchi T. A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9. J Biol Chem. 2009 Jan 9;284(2):733-9. doi: 10.1074/jbc.M804994200. Epub 2008 Nov , 14. PMID:19010785 doi:http://dx.doi.org/10.1074/jbc.M804994200
10. ↑ Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J, Helin K. JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature. 2010 Jan 14. PMID:20075857 doi:http://dx.doi.org/nature08788