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

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. 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

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.