JARID2

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Jarid2 (jumonji, AT rich interactive domain 2) is a protein coding gene that functions as a putative transcription factor. Distinguished as a nuclear protein necessary for mouse embryogenesis, Jarid2 is a member of the jumonji family that contains a DNA binding domain known as the AT-rich interaction domain (ARID)[2, 8, 11, 13]. In vitro studies of Jarid2 reveal that ARID along with other functional domains are involved in DNA binding, nuclear localization, transcriptional repression [5], and recruitment of Polycomb-repressive complex 2 (PRC2) [9, 10]. Intracellular mechanisms underlying these interactions remain largely unknown.

In search of developmentally important genes, Jarid2 has previously been identified by gene trap technology as an important factor necessary for organ development [2, 3, 5]. During mouse organogenesis, Jarid2 is involved in the formation of the neural tube and development of the liver, spleen, thymus and cardiovascular system [6, 12]. Continuous Jarid2 expression in the tissues of the heart, highlight its presiding role in the development of both the embryonic and the adult heart [2]. Mutant models of Jarid2 embryos show severe heart malformations, ventricular septal defects, noncompaction of the ventricular wall, and dialated atria [4]. Homozygous mutants of Jarid2 are found to die soon after birth [4]. Overexpression of the mouse Jarid2 gene has been reported to repress cardiomyocyte proliferation through it close interaction with retinoblastoma protein (Rb), a master cell cycle regulator [3, 5, 7]. Retinoblastoma-binding protein-2 and the human SMCX protein share regions of homology between mice and humans [1, 14].

Model organisms[edit]

Model organisms have been used in the study of JARID2 function. A conditional knockout mouse line, called Jarid2tm1a(KOMP)Wtsi[5][6] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[7][8][9]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[3][10] Twenty six tests were carried out and two phenotypes were reported. Homozygous mutant embryos were identified during gestation but almost half showed signs of oedema, and in a separate study, only 1% survived until weaning (significantly less than the Mendelian ratio). The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[3]

References[edit]

  1. ^ "Salmonella infection data for Jarid2". Wellcome Trust Sanger Institute. 
  2. ^ "Citrobacter infection data for Jarid2". Wellcome Trust Sanger Institute. 
  3. ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. 
  4. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  5. ^ "International Knockout Mouse Consortium". 
  6. ^ "Mouse Genome Informatics". 
  7. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  8. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  9. ^ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  10. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 


1. Bergé-Lefranc, J. L., Jay, P., Massacrier, A., Cau, P., Mattei, M. G., Bauer, S., . . . Fontes, M. (1996). Characterization of the human jumonji gene. Human Molecular Genetics, 5(10), 1637-41.

2. Jung, J., Kim, T. G., Lyons, G. E., Kim, H. R., & Lee, Y. (2005). Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma protein. The Journal of Biological Chemistry, 280(35), 30916-23.

3. Jung, J., Mysliwiec, M. R., & Lee, Y. (2005). Roles of JUMONJI in mouse embryonic development. Developmental Dynamics : An Official Publication of the American Association of Anatomists, 232(1), 21-32.

4. Kim, T. G., Kraus, J. C., Chen, J., & Lee, Y. (2003). JUMONJI, a critical factor for cardiac development, functions as a transcriptional repressor. The Journal of Biological Chemistry, 278(43), 42247-55.

5. Klassen, S. S., & Rabkin, S. W. (2008). Nitric oxide induces gene expression of jumonji and retinoblastoma 2 protein while reducing expression of atrial natriuretic peptide precursor type B in cardiomyocytes. Folia Biologica, 54(2), 65-70.

6. Motoyama, J., Kitajima, K., Kojima, M., Kondo, S., & Takeuchi, T. (1997). Organogenesis of the liver, thymus and spleen is affected in jumonji mutant mice. Mechanisms of Development, 66(1-2), 27-37.

7. Mysliwiec, M. R., Chen, J., Powers, P. A., Bartley, C. R., Schneider, M. D., & Lee, Y. (2006). Generation of a conditional null allele of jumonji. Genesis (New York, N.Y. : 2000), 44(9), 407-11.

8. Mysliwiec, M. R., Kim, T. G., & Lee, Y. (2007). Characterization of zinc finger protein 496 that interacts with jumonji/jarid2. FEBS Letters, 581(14), 2633-40.

9. Pasini, D., Cloos, P. A., Walfridsson, J., Olsson, L., Bukowski, J. P., Johansen, J. V., . . . Helin, K. (2010). JARID2 regulates binding of the polycomb repressive complex 2 to target genes in ES cells. Nature, 464(7286), 306-10.

10. Son, J., Shen, S. S., Margueron, R., & Reinberg, D. (2013). Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin. Genes & Development, 27(24), 2663-77.

11. Takahashi, M., Kojima, M., Nakajima, K., Suzuki-Migishima, R., Motegi, Y., Yokoyama, M., & Takeuchi, T. (2004). Cardiac abnormalities cause early lethality of jumonji mutant mice. Biochemical and Biophysical Research Communications, 324(4), 1319-23.

12. Takeuchi, T., Yamazaki, Y., Katoh-Fukui, Y., Tsuchiya, R., Kondo, S., Motoyama, J., & Higashinakagawa, T. (1995). Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. Genes & Development, 9(10), 1211-22.

13. Toyoda, M., Kojima, M., & Takeuchi, T. (2000). Jumonji is a nuclear protein that participates in the negative regulation of cell growth. Biochemical and Biophysical Research Communications, 274(2), 332-6.

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.