Chromatin Regulator Cistrome

Chromatin Regulator

Alias

KDM6B

JMJD3

External Links:

Wiki GeneCards NCBI UniProt

Related histone modifications:

H3K27me3;H3K27me2

Introduction

Full name: Lysine (K)-specific demethylase 6B . KDM6B has been shown to decrease the level of both di- and trimethylation on histone H3K27 (1). KDM6B is a Jmjc-domain-containing demethylase that is responsible for activating certain genes by demethylating the H3K27 marks on their promoters, thereby playing a role in gene transcription regulation, differentiation, development, cell death, and signaling pathways (1-4).

Function and Interaction

JMJD3 (KDM6B) overexpression can dramatically reduce the level of trimethylation on histone H3K27, thus affecting the regulation of polycomb proteins and Hox genes (5). JMJD3 is essential for the differentiation of neural lineages and neurogenesis and may also participate in antigen-driven B-cell differentiation (2-3). It binds to the INK4A-ARF locus, thereby modulating the transcription of p16INK4A and p14ARF, which are important tumor repressor proteins (6). KDM6B is induced by vitamin D and NF-kB in response to some stimuli, hence being involved in several signaling pathways (4,7). KDM6B is required for the differentiation of bone marrow macrophages and M2 macrophage polarization, which is important in anti-bacterial processes (8). Together with UTX, KDM6B can regulate interactions between the T-box family and the Brg1-containing SWI/SNF complex, which is essential for Ifng remodeling in differentiated Th1 cells (9). KDM6B can interact with p53 to regulate its expression during neurogenesis through ARF (10). KDM6B interacts with Smads2/3 and is recruited to their target genes via the Nodal signaling pathway (11).

Disease Association

KDM6B is overexpressed in HodgkinÕs Lymphoma, which is caused by the Epstein-Barr virus (3). KDM6B plays a regulatory role in colon cancer cells (7) and is capable of regulating the expression of hematopoietic progenitor kinase 1in systemic lupus erythematosus T cells (12).

ChIP-Seq data

Species	Cell line	Cell type	Tissue	Data	Download	Send to Cistrome	Analysis Figures	Comparison	Reference
Mus musculus	NA	Embryonic Stem Cell	Embryo	GSE42155 ,GSM1207794		Click Download	Click	24074864

ChIP-Seq data of related histone modifications

Products/Substrates	Species	Cell line	Cell type	Tissue	Data	Download	Analysis Figures	Reference
H3K27me3	Mus musculus	NA	Embryonic Stem Cell	Embryo	GSE38164 ,GSM1001323	Bed Big wiggle	Click Download	23352811
H3K27me3	Mus musculus	NA	Embryonic Stem Cell	Embryo	GSE38164 ,GSM1001325	Bed Big wiggle	Click Download	23352811
H3K27me3	Mus musculus	NA	Embryonic Stem Cell	Embryo	GSE38164 ,GSM1001327	Bed Big wiggle	Click Download	23352811
H3K27me3	Mus musculus	V6.5	Embryonic Stem Cell	Embryo	GSE47485 ,GSM1151029	Bed Big wiggle	Click Download	23955559
H3K27me3	Homo sapiens	CUTLL1	T Lymphocyte	Blood	GSE56696 ,GSM1366928	Bed Big wiggle	Click Download	25132549
H3K27me3	Homo sapiens	CUTLL1	T Lymphocyte	Blood	GSE56696 ,GSM1366929	Bed Big wiggle	Click Download	25132549
H3K27me3	Mus musculus	E14	Embryonic Stem Cell	Embryo	GSE58023 ,GSM1399503	Bed Big wiggle	Click Download	24999238
H3K27me3	Mus musculus	E14	Embryonic Stem Cell	Embryo	GSE58023 ,GSM1399504	Bed Big wiggle	Click Download	24999238
H3K27me3	Mus musculus	E14	Embryonic Stem Cell	Embryo	GSE58023 ,GSM1399505	Bed Big wiggle	Click Download	24999238
H3K27me3	Mus musculus	TNGA	Embryonic Stem Cell	Embryo	GSE23943 ,GSM590114	Bed Big wiggle	Click Download	22541430
H3K27me3	Homo sapiens	CUTLL1	T Lymphocyte	Blood	GSE29600 ,GSM732912	Bed Big wiggle	Click Download	21737748
H3K27me3	Mus musculus	V6.5	Embryonic Stem Cell	Embryo	GSE28254 ,GSM821394	Bed Big wiggle	Click Download	22466170
H3K27me3	Mus musculus	CMTi-1	Embryonic Stem Cell	Embryo	GSE34483 ,GSM849942	Bed Big wiggle	Click Download	23260488
H3K27me3	Mus musculus	R1	Embryonic Stem Cell	Embryo	GSE36294 ,GSM886505	Bed Big wiggle	Click Download	24381111
H3K27me3	Mus musculus	V6.5	Embryonic Stem Cell	Embryo	GSE40065 ,GSM984546	Bed Big wiggle	Click Download	23990805

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1. Hong, S.H., Cho, Y.W., Yu, L.R., Yu, H., Veenstra, T.D. and Ge, K. (2007) Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. P Natl Acad Sci USA, 104, 18439-18444.
2. Burgold, T., Spreafico, F., De Santa, F., Totaro, M.G., Prosperini, E., Natoli, G. and Testa, G. (2008) The Histone H3 Lysine 27-Specific Demethylase Jmjd3 Is Required for Neural Commitment. PLoS One, 3.
3. Anderton, J.A., Bose, S., Vockerodt, M., Vrzalikova, K., Wei, W., Kuo, M., Helin, K., Christensen, J., Rowe, M., Murray, P.G. et al. (2011) The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma. Oncogene, 30, 2037-2043.
4. Das, N.D., Jung, K.H., Choi, M.R., Yoon, H.S., Kim, S.H. and Chai, Y.G. (2012) Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line. Cell Biochem Funct, 30, 224-232.
5. Agger, K., Cloos, P.A.C., Christensen, J., Pasini, D., Rose, S., Rappsilber, J., Issaeva, I., Canaani, E., Salcini, A.E. and Helin, K. (2007) UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature, 449, 731-U710.
6. Agger, K., Cloos, P.A.C., Rudkjaer, L., Williams, K., Andersen, G., Christensen, J. and Helin, K. (2009) The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Gene Dev, 23, 1171-1176.
7. Pereira, F., Barbachano, A., Silva, J., Bonilla, F., Campbell, M.J., Munoz, A. and Larriba, M.J. (2011) KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects in colon cancer cells. Hum Mol Genet, 20, 4655-4665.
8. Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T. et al. (2010) The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol, 11, 936-U989.
9. Miller, S.A., Mohn, S.E. and Weinmann, A.S. (2010) Jmjd3 and UTX Play a Demethylase-Independent Role in Chromatin Remodeling to Regulate T-Box Family Member-Dependent Gene Expression. Mol Cell, 40, 594-605.
10. Sola, S., Xavier, J.M., Santos, D.M., Aranha, M.M., Morgado, A.L., Jepsen, K. and Rodrigues, C.M.P. (2011) p53 Interaction with JMJD3 Results in Its Nuclear Distribution during Mouse Neural Stem Cell Differentiation. PLoS One, 6.
11. Dahle, O., Kumar, A. and Kuehn, M.R. (2010) Nodal Signaling Recruits the Histone Demethylase Jmjd3 to Counteract Polycomb-Mediated Repression at Target Genes. Sci Signal, 3.
12. Zhang, Q., Long, H., Liao, J.Y., Zhao, M., Liang, G.P., Wu, X.Y., Zhang, P., Ding, S., Luo, S.Y. and Lu, Q.J. (2011) Inhibited expression of hematopoietic progenitor kinase 1 associated with loss of jumonji domain containing 3 promoter binding contributes to autoimmunity in systemic lupus erythematosus. J Autoimmun, 37, 180-189.

Chromatin Regulator Cistrome
A knowledgebase for chromatin modifying enzymes and chromatin remodelers