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. The biological roles JHDM genes have been shown to potentially playing a role in cancer. 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. 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. Further research needs to be done to determine Jarid1B function in cancer development and its function as a histone demethylase.
^Lahoud MH, Ristevski S, Venter DJ, Jermiin LS, Bertoncello I, Zavarsek S, Hasthorpe S, Drago J, de Kretser D, Hertzog PJ, Kola I (Aug 2001). "Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs". Genome Research11 (8): 1327–34. doi:10.1101/gr.168801. PMID11483573.
^Zhu L, Hu J, Lin D, Whitson R, Itakura K, Chen Y (Aug 2001). "Dynamics of the Mrf-2 DNA-binding domain free and in complex with DNA". Biochemistry40 (31): 9142–50. doi:10.1021/bi010476a. PMID11478881.
^Kristensen, L. H., Nielsen, A. L., Helgstrand, C., Lees, M., Cloos, P., Kastrup, J. S., . . . Gajhede, M. (2012). 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. FEBS J, 279(11), 1905-1914. doi: 10.1111/j.1742-4658.2012.08567.x
^Zou, M. R., Cao, J., Liu, Z., Huh, S. J., Polyak, K., & Yan, Q. (2014). Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. J Biol Chem, 289(25), 17620-17633. doi: 10.1074/jbc.M114.570853
^Albert, M., Schmitz, S. U., Kooistra, S. M., Malatesta, M., Morales Torres, C., Rekling, J. C., . . . Helin, K. (2013). The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3. PLoS Genet, 9(4), e1003461. doi: 10.1371/journal.pgen.1003461
^ abTan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS (Jun 2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9". The Journal of Biological Chemistry278 (23): 20507–13. doi:10.1074/jbc.M301994200. PMID12657635.
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 (May 1999). "A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer". The Journal of Biological Chemistry274 (22): 15633–45. doi:10.1074/jbc.274.22.15633. PMID10336460.
Kashuba V, Protopopov A, Podowski R, Gizatullin R, Li J, Klein G, Wahlestedt C, Zabarovsky E (Jun 2000). "Isolation and chromosomal localization of a new human retinoblastoma binding protein 2 homologue 1a (RBBP2H1A)". European Journal of Human Genetics8 (6): 407–13. doi:10.1038/sj.ejhg.5200474. PMID10878660.
Barrett A, Madsen B, Copier J, Lu PJ, Cooper L, Scibetta AG, Burchell J, Taylor-Papadimitriou J (Oct 2002). "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. Journal International Du Cancer101 (6): 581–8. doi:10.1002/ijc.10644. PMID12237901.
Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS (Jun 2003). "Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9". The Journal of Biological Chemistry278 (23): 20507–13. doi:10.1074/jbc.M301994200. PMID12657635.
Tzschach A, Lenzner S, Moser B, Reinhardt R, Chelly J, Fryns JP, Kleefstra T, Raynaud M, Turner G, Ropers HH, Kuss A, Jensen LR (Apr 2006). "Novel JARID1C/SMCX mutations in patients with X-linked mental retardation". Human Mutation27 (4): 389. doi:10.1002/humu.9420. PMID16541399.
Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y (Mar 2007). "PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation". Molecular Cell25 (6): 801–12. doi:10.1016/j.molcel.2007.03.001. PMID17363312.
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 (Jul 2007). "Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases". International Journal of Cancer. Journal International Du Cancer121 (2): 265–75. doi:10.1002/ijc.22673. PMID17373667.