JARID1B explained

Lysine-specific demethylase 5B also known as histone demethylase JARID1B is a demethylase enzyme that in humans is encoded by the KDM5B gene.^{[1] [2] [3]} JARID1B belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.

Function

Jarid1B (also known as KDM5B or PLU1) is in the family of JHDM genes. These are responsible for demethylation of tri- and di-methylated lysines in the 4 position of histone 3 (H3K4me3 and H3K4me2). Jarid1B is a multidomain enzyme that is part of the subfamily KDM5. The whole Jarid1 family is a protein family that possesses H3K4 histone demethylase activity.^[4]

Jarid1B has been implicated in the development of prostate, breast, and skin cancer and also has been associated with melanoma maintenance. Knockout mice (Jarid1b−/−) produced are viable in neonatal life. These mice do exhibit the phenotype of premature mortality, decreased fertility in female mice, reduction in body weight and impairment in mammary gland development. It also acted to decrease serum estrogen levels and caused reduced mammary epithelial cell proliferation in the early stages of puberty. These Jarid1b−/− mice seem to be greatly affected in many regulators of the development of mammy development such as FOXA1 and estrogen receptor α.^[5] However, others have shown that a Jarid1B knockout embryos usually have neonatal lethality due to the failure of their respiratory system. Knockout embryos have also been seen to have several different neural defects including: disorganized cranial nerves, increased incidences of exencephaly, and defects in eye development.^[6]

Interactions

JARID1B has been shown to interact with FOXG1^[7] and PAX9.^[7]

Further reading

• Lu PJ, Sundquist K, Baeckstrom D, Poulsom R, Hanby A, Meier-Ewert S, Jones T, Mitchell M, Pitha-Rowe P, Freemont P, Taylor-Papadimitriou J . A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer . The Journal of Biological Chemistry . 274 . 22 . 15633–45 . May 1999 . 10336460 . 10.1074/jbc.274.22.15633 . free .
• Kashuba V, Protopopov A, Podowski R, Gizatullin R, Li J, Klein G, Wahlestedt C, Zabarovsky E . Isolation and chromosomal localization of a new human retinoblastoma binding protein 2 homologue 1a (RBBP2H1A) . European Journal of Human Genetics . 8 . 6 . 407–13 . June 2000 . 10878660 . 10.1038/sj.ejhg.5200474 . free .
• Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J . PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? . International Journal of Cancer . 101 . 6 . 581–8 . October 2002 . 12237901 . 10.1002/ijc.10644 . free .
• Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS . Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9 . The Journal of Biological Chemistry . 278 . 23 . 20507–13 . June 2003 . 12657635 . 10.1074/jbc.M301994200 . free .
• Patsialou A, Wilsker D, Moran E . DNA-binding properties of ARID family proteins . Nucleic Acids Research . 33 . 1 . 66–80 . 2005 . 15640446 . 546134 . 10.1093/nar/gki145 .
• Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR . Novel JARID1C/SMCX mutations in patients with X-linked mental retardation . Human Mutation . 27 . 4 . 389 . April 2006 . 16541399 . 10.1002/humu.9420 . free .
• Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y . PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation . Molecular Cell . 25 . 6 . 801–12 . March 2007 . 17363312 . 10.1016/j.molcel.2007.03.001 . free .
• Barrett A, Santangelo S, Tan K, Catchpole S, Roberts K, Spencer-Dene B, Hall D, Scibetta A, Burchell J, Verdin E, Freemont P, Taylor-Papadimitriou J . Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases . International Journal of Cancer . 121 . 2 . 265–75 . July 2007 . 17373667 . 10.1002/ijc.22673 . 24855452 .

Notes and References

1. Lahoud MH, Ristevski S, Venter DJ, Jermiin LS, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog PJ, Kola I . Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs . Genome Research . 11 . 8 . 1327–34 . August 2001 . 11483573 . 10.1101/gr.168801 . free . 10536/DRO/DU:30121320 . free .
2. Zhu L, Hu J, Lin D, Whitson R, Itakura K, Chen Y . Dynamics of the Mrf-2 DNA-binding domain free and in complex with DNA . Biochemistry . 40 . 31 . 9142–50 . August 2001 . 11478881 . 10.1021/bi010476a .
3. Web site: Entrez Gene: JARID1B jumonji, AT rich interactive domain 1B.
4. Kristensen LH, Nielsen AL, Helgstrand C, Lees M, Cloos P, Kastrup JS, Helin K, Olsen L, Gajhede M . Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor . The FEBS Journal . 279 . 11 . 1905–14 . June 2012 . 22420752 . 10.1111/j.1742-4658.2012.08567.x . free .
5. Zou MR, Cao J, Liu Z, Huh SJ, Polyak K, Yan Q . Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes . The Journal of Biological Chemistry . 289 . 25 . 17620–33 . June 2014 . 24802759 . 4067197 . 10.1074/jbc.M114.570853 . free .
6. Albert M, Schmitz SU, Kooistra SM, Malatesta M, Morales Torres C, Rekling JC, Johansen JV, Abarrategui I, Helin K . The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3 . PLOS Genetics . 9 . 4 . e1003461 . April 2013 . 23637629 . 3630093 . 10.1371/journal.pgen.1003461 . free .
7. Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS . Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9 . The Journal of Biological Chemistry . 278 . 23 . 20507–13 . June 2003 . 12657635 . 10.1074/jbc.M301994200 . free .