CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

KDM2BCXXC2;FBXL10;Fbl10;JHDM1B;PCCX2;NDY1

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K36me2;H3K4me3;H3K36me1

Introduction

Full name: Lysine (K)-specific demethylase 2B. KDM2B/FBXL10 is a protein of multi-domains, including a JmjC domain situated at the N-terminal region of the protein, followed by a CXXC domain, a PHD domain, a F-box motif and seven leucine-rich repeats,plays an essential role in cell growth,stem cell self-renewal,somatic cell reprogramming,suppression of premature cellular senescence,maintenance of mouse embryonic stem cell pluripotency and tumorigenesis(1,3,4,5,6,10).KDM2B can de-methylate di-methylation on histone H3K36(H3K36me2) and tri-methylation on histone H3K4(H3K4me3)(2,7,8).

Function and Interaction

KDM2B catalyzes demethylation through JmjC domain,recognizes CpG islands and recruits the polycomb repressive complex1 through CxxC zinc-finger and fuctions as a subunit of the CUL1-RING ubiquitin ligase(CRL1/SCFKDM2B) complex to regulate c-Fos pretein levels(1).KDM2B interacts with the core components of polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes to repress their expression(10).KDM2B facilitates iPSC generation in an enzymatic-activity-dependent relying on its demethylase and DNA-binding activities that contribute to the activation of the reprogramming transcription program in the early stage(4).KDM2B targets the p15(Ink4b) locus and regulates its expression in an enzymatic activity-dependent manner to regulate cell proliferation and senescence(9).NDY1/KDM2B functions as a master regulator of a set of miRNAs that target several members of the polycomb complexes PRC1 and PRC2 and controls self-renewal of breast cancer stem cells(5).KDM2B is also found to interact with SKP1 via its F-box domain,a linker protein involved in the assembly of the SCF(SKP1-CUL1-F-box) E3 ubiquitin ligase complex(11,12).

Disease Association

KDM2B is overexpressed in human T-cell and B-cell acute lymphoblastic leukemia,acute myeloid leukemia,seminomas,and mammary and pancreatic adenocarcinomas,strong suggest that KDM2B functions as an oncogene,in primary human breast cancer, NDY1/KDM2B expression correlates negatively with the expression of the NDY1-regulated miRNAs and positively with the expression of their PRC targets(5).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Mus musculus3T3-L1PreadipocyteAdiposeGSE64312 ,GSM1568457
Click  DownloadClick25533466

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K36me2 Mus musculus NA Embryonic Stem Cell Embryo GSE43231 ,GSM1059000 Bed     Big wiggle
Click   Download24361252
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171628 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171630 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE48172 ,GSM1171632 Bed     Big wiggle
Click   Download23934151
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1258237 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE52071 ,GSM1276704 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE52071 ,GSM1276705 Bed     Big wiggle
Click   Download24423662
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282137 Bed     Big wiggle
Click   Download24495580
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282139 Bed     Big wiggle
Click   Download24495580
H3K4me3 Homo sapiens None Stem cell Blood GSE54580 ,GSM1612049 Bed     Big wiggle
Click   Download26748712
H3K4me3 Homo sapiens None Stem cell Blood GSE54580 ,GSM1612062 Bed     Big wiggle
Click   Download26748712
H3K4me3 Homo sapiens None Myeloid Cell None GSE54580 ,GSM1612068 Bed     Big wiggle
Click   Download26748712
H3K4me3 Homo sapiens None Stem cell Blood GSE54580 ,GSM1612070 Bed     Big wiggle
Click   Download26748712
H3K4me3 Homo sapiens None Myeloid Cell None GSE54580 ,GSM1612071 Bed     Big wiggle
Click   Download26748712
H3K4me3 Homo sapiens None Myeloid Cell None GSE54580 ,GSM1612075 Bed     Big wiggle
Click   Download26748712
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397402 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397403 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus XT67E1 Embryonic Stem Cell Embryo GSE15884 ,GSM397404 Bed     Big wiggle
Click   Download19581487
H3K4me3 Mus musculus C6 Embryonic Stem Cell Embryo GSE16893 ,GSM487545 Bed     Big wiggle
Click   Download20211137
H3K4me3 Mus musculus C6 Embryonic Stem Cell Embryo GSE16893 ,GSM487548 Bed     Big wiggle
Click   Download20211137
H3K4me3 Mus musculus TNGA Embryonic Stem Cell Embryo GSE23943 ,GSM590110 Bed     Big wiggle
Click   Download22541430
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE26136 ,GSM651193 Bed     Big wiggle
Click   Download21335234
H3K4me3 Mus musculus CMTi-1 Embryonic Stem Cell Embryo GSE34483 ,GSM849941 Bed     Big wiggle
Click   Download23260488
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886518 Bed     Big wiggle
Click   Download24381111
H3K4me3 Mus musculus TC1 Embryonic Stem Cell Embryo GSE37776 ,GSM928131 Bed     Big wiggle
Click   Download22666422
H3K4me3 Mus musculus 3.2N Embryonic Stem Cell Embryo GSE37776 ,GSM928132 Bed     Big wiggle
Click   Download22666422
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE39472 ,GSM969829 Bed     Big wiggle
Click   Download22826230
H3K4me3 Mus musculus NA Embryonic Stem Cell Embryo GSE39472 ,GSM969830 Bed     Big wiggle
Click   Download22826230
H3K4me3 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970227 Bed     Big wiggle
Click   Download24289921
H3K4me3 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970228 Bed     Big wiggle
Click   Download24289921

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.Han, X.R., Zha, Z., Yuan, H.X., Feng, X., Xia, Y.K., Lei, Q.Y., Guan, K.L., and Xiong, Y. (2016). KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation. Oncogene 35, 4179-4190.
2.He, J., Nguyen, A.T., and Zhang, Y. (2011). KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia. Blood 117, 3869-3880.
3.Wong, S.J., Gearhart, M.D., Taylor, A.B., Nanyes, D.R., Ha, D.J., Robinson, A.K., Artigas, J.A., Lee, O.J., Demeler, B., Hart, P.J., et al. (2016). KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1. Structure 24, 1795-1801.
4.Liang, G., He, J., and Zhang, Y. (2012). Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming. Nat Cell Biol 14, 457-466.
5.Kottakis, F., Foltopoulou, P., Sanidas, I., Keller, P., Wronski, A., Dake, B.T., Ezell, S.A., Shen, Z., Naber, S.P., Hinds, P.W., et al. (2014). NDY1/KDM2B functions as a master regulator of polycomb complexes and controls self-renewal of breast cancer stem cells. Cancer Res 74, 3935-3946.
6.Farcas, A.M., Blackledge, N.P., Sudbery, I., Long, H.K., McGouran, J.F., Rose, N.R., Lee, S., Sims, D., Cerase, A., Sheahan, T.W., et al. (2012). KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands. Elife 1, e00205.
7.Rohde, M., Sievers, E., Janzer, A., Willmann, D., Egert, A., Schorle, H., Schule, R., and Kirfel, J. (2016). Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts. Exp Cell Res 348, 123-131.
8.Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., and Pagano, M. (2007). JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature 450, 309-313.
9.He, J., Kallin, E.M., Tsukada, Y., and Zhang, Y. (2008). The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat Struct Mol Biol 15, 1169-1175.
10.He, J., Shen, L., Wan, M., Taranova, O., Wu, H., and Zhang, Y. (2013). Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes. Nat Cell Biol 15, 373-384.
11.Gearhart, M.D., Corcoran, C.M., Wamstad, J.A., and Bardwell, V.J. (2006). Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol Cell Biol 26, 6880-6889.
12.Koyama-Nasu, R., David, G., and Tanese, N. (2007). The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun. Nat Cell Biol 9, 1074-1080.

Figure Gallery

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.

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