JARID2

Protein Jumonji is a protein that in humans is encoded by the JARID2 gene.[5][6] JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.

JARID2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5HYN
Identifiers
Aliases	JARID2, JMJ, jumonji and AT-rich interaction domain containing 2
External IDs	OMIM: 601594 MGI: 104813 HomoloGene: 31279 GeneCards: JARID2
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p22.3 Start 15,246,069 bp[1] End 15,522,042 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A5|13 21.66 cM Start 44,729,474 bp[2] End 44,921,643 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • chromatin binding • histone demethylase activity • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • transcription factor binding • GO:0001948 protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • methylated histone binding • histone demethylase activity (H3-trimethyl-K4 specific) Cellular component • ESC/E(Z) complex • nucleoplasm • cell nucleus • histone methyltransferase complex • mitochondrion Biological process • cell differentiation • negative regulation of histone methylation • regulation of transcription, DNA-templated • thymus development • negative regulation of transcription from RNA polymerase II promoter • spleen development • transcription, DNA-templated • stem cell differentiation • multicellular organism development • central nervous system development • negative regulation of gene expression, epigenetic • regulation of cell proliferation • liver development • negative regulation of transcription, DNA-templated • negative regulation of cell proliferation • positive regulation of histone H3-K9 methylation • negative regulation of cardiac muscle hypertrophy • cellular response to leukemia inhibitory factor • negative regulation of cardiac muscle cell proliferation • chromatin organization • histone demethylation • chromatin remodeling • histone H3-K4 demethylation, trimethyl-H3-K4-specific Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3720	16468
Ensembl	ENSG00000008083	ENSMUSG00000038518
UniProt	Q92833	Q62315
RefSeq (mRNA)	NM_001267040 NM_004973	NM_001205043 NM_001205044 NM_021878 NM_001360281
RefSeq (protein)	NP_001253969 NP_004964	NP_001191972 NP_001191973 NP_068678 NP_001347210
Location (UCSC)	Chr 6: 15.25 – 15.52 Mb	Chr 13: 44.73 – 44.92 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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).[7][8][9][10] In vitro studies of Jarid2 reveal that ARID along with other functional domains are involved in DNA binding, nuclear localization, transcriptional repression,[11] and recruitment of Polycomb-repressive complex 2 (PRC2).[12][13] 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.[7][11][14] During mouse organogenesis, Jarid2 is involved in the formation of the neural tube and development of the liver, spleen, thymus and cardiovascular system.[15][16] Continuous Jarid2 expression in the tissues of the heart, highlight its presiding role in the development of both the embryonic and the adult heart.[7] Mutant models of Jarid2 embryos show severe heart malformations, ventricular septal defects, noncompaction of the ventricular wall, and atrial enlargement.[7] Homozygous mutants of Jarid2 are found to die soon after birth.[7] 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.[11][14][17] Retinoblastoma-binding protein-2 and the human SMCX protein share regions of homology between mice and humans.[5]

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[18]
Citrobacter infection	Normal[19]
All tests and analysis from[20][21]

Model organisms have been used in the study of JARID2 function. A conditional knockout mouse line, called Jarid2^{tm1a(KOMP)Wtsi}[22][23] 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.[24][25][26]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[20][27] 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.[20]

References

1. GRCh38: Ensembl release 89: ENSG00000008083 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038518 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: JARID2 jumonji, AT rich interactive domain 2".
7. 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.
8. Mysliwiec MR, Kim TG, Lee Y (2007). "Characterization of zinc finger protein 496 that interacts with jumonji/jarid2". FEBS Letters. 581 (14): 2633–40. doi:10.1016/j.febslet.2007.05.006. PMC 2002548. PMID 17521633.
9. 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. doi:10.1016/j.bbrc.2004.09.203. PMID 15504358.
10. 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. doi:10.1006/bbrc.2000.3138. PMID 10913339.
11. Klassen SS, Rabkin SW (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. PMID 18498724.
12. Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Helin K (2010). "JARID2 regulates binding of the polycomb repressive complex 2 to target genes in ES cells". Nature. 464 (7286): 306–10. doi:10.1038/nature08788. PMID 20075857.
13. Son J, Shen SS, 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. doi:10.1101/gad.225888.113. PMC 3877756. PMID 24352422.
14. Jung J, Mysliwiec MR, Lee Y (2005). "Roles of Jumonji in mouse embryonic development". Developmental Dynamics. 232 (1): 21–32. doi:10.1002/dvdy.20204. PMID 15580614.
15. 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. doi:10.1016/s0925-4773(97)00082-8. PMID 9376320.
16. 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. doi:10.1101/gad.9.10.1211. PMID 7758946.
17. Mysliwiec MR, Chen J, Powers PA, Bartley CR, Schneider MD, Lee Y (2000). "Generation of a conditional null allele of jumonji". Genesis. 44 (9): 407–11. doi:10.1002/dvg.20221. PMC 2002517. PMID 16900512.
18. "Salmonella infection data for Jarid2". Wellcome Trust Sanger Institute.
19. "Citrobacter infection data for Jarid2". Wellcome Trust Sanger Institute.
20. 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.
21. Mouse Resources Portal, Wellcome Trust Sanger Institute.
22. "International Knockout Mouse Consortium".
23. "Mouse Genome Informatics".
24. 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.
25. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
26. 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.
27. 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.

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.
• 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.