JARID2

Jumonji, AT rich interactive domain 2
Identifiers
Symbols	JARID2 ; JMJ
External IDs	OMIM: 601594 MGI: 104813 HomoloGene: 31279 GeneCards: JARID2 Gene
Gene ontology Molecular function • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding • chromatin binding • histone demethylase activity Cellular component • nucleus • nucleoplasm • histone methyltransferase complex • ESC/E(Z) complex Biological process • negative regulation of transcription from RNA polymerase II promoter • liver development • transcription, DNA-templated • central nervous system development • negative regulation of cell proliferation • gene expression • chromatin modification • negative regulation of histone methylation • regulation of gene expression, epigenetic • negative regulation of gene expression, epigenetic • negative regulation of transcription, DNA-templated • spleen development • thymus development • stem cell differentiation • positive regulation of histone H3-K9 methylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3720	16468
Ensembl	ENSG00000008083	ENSMUSG00000038518
UniProt	Q92833	Q62315
RefSeq (mRNA)	NM_001267040	NM_001205043
RefSeq (protein)	NP_001253969	NP_001191972
Location (UCSC)	Chr 6: 15.25 – 15.52 Mb	Chr 13: 44.73 – 44.92 Mb
PubMed search

Protein Jumonji is a protein that in humans is encoded by the JARID2 gene.^[1][2]

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 dilated 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

Jarid2 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[3]
Citrobacter infection	Normal[4]
All tests and analysis from[5][6]

Model organisms have been used in the study of JARID2 function. A conditional knockout mouse line, called Jarid2^{tm1a(KOMP)Wtsi[7][8]} 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.^[9][10][11]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[5][12] 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.^[5]

References

1. Berge-Lefranc JL, Jay P, Massacrier A, Cau P, Mattei MG, Bauer S, Marsollier C, Berta P, Fontes M (Feb 1997). "Characterization of the human jumonji gene". Hum Mol Genet 5 (10): 1637–41. doi:10.1093/hmg/5.10.1637. PMID 8894700.
2. "Entrez Gene: JARID2 jumonji, AT rich interactive domain 2".
3. "Salmonella infection data for Jarid2". Wellcome Trust Sanger Institute.
4. "Citrobacter infection data for Jarid2". Wellcome Trust Sanger Institute.
5. 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.
6. Mouse Resources Portal, Wellcome Trust Sanger Institute.
7. "International Knockout Mouse Consortium".
8. "Mouse Genome Informatics".
9. 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.
10. Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
11. 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.
12. 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, 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.

Further reading

• Lee Y, Song AJ, Baker R, et al. (2000). "Jumonji, a nuclear protein that is necessary for normal heart development.". Circ. Res. 86 (9): 932–8. doi:10.1161/01.res.86.9.932. PMID 10807864.
• Toyoda M, Kojima M, Takeuchi T (2000). "Jumonji is a nuclear protein that participates in the negative regulation of cell growth.". Biochem. Biophys. Res. Commun. 274 (2): 332–6. doi:10.1006/bbrc.2000.3138. PMID 10913339.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Kim TG, Kraus JC, Chen J, Lee Y (2004). "JUMONJI, a critical factor for cardiac development, functions as a transcriptional repressor.". J. Biol. Chem. 278 (43): 42247–55. doi:10.1074/jbc.M307386200. PMID 12890668.
• Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6.". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
• Volcik KA, Zhu H, Finnell RH, et al. (2004). "Evaluation of the jumonji gene and risk for spina bifida and congenital heart defects.". Am. J. Med. Genet. A 126 (2): 215–7. doi:10.1002/ajmg.a.20574. PMID 15057990.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Kim TG, Chen J, Sadoshima J, Lee Y (2005). "Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors.". Mol. Cell. Biol. 24 (23): 10151–60. doi:10.1128/MCB.24.23.10151-10160.2004. PMC 529025. PMID 15542826.
• Pedrosa E, Ye K, Nolan KA, et al. (2007). "Positive association of schizophrenia to JARID2 gene.". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (1): 45–51. doi:10.1002/ajmg.b.30386. PMID 16967465.

External links

• JARID2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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