CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

KDM5ARBP2; RBBP2; RBBP-2; JARID1A

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K4me2;H3K4me3

Introduction

Full name: Lysine (K)-specific demethylase 5A . KDM5A (also known as RBP2), which was first detected as a retinoblastoma-binding protein, is a member of the Jumonji (Jmj) C domain-containing family and is distinguished from most other histone-modifying enzymes based on binding to DNA through its ARID domain. It plays an essential role in transcriptional regulation, cell differentiation, and development (1-4). KDM5A can specifically remove the di- and trimethylation of histone H3K4 (2,5).

Function and Interaction

KDM5A binds to the promoter regions of many differentiation-related genes, thereby regulating their transcription through its demethylation function (4). KDM5A co-binds with pRB (the RB-1 tumor-suppressor gene product), thus modulating the transcription and differentiation processes (6). KDM5A can be recruited by Polycomb-Repressive Complex 2 to its development-related target genes, suppressing their transcription (7). It is also required for the regulation of the progesterone receptor (8). KDM5A interacts with RBP-J protein, which is of vital importance in Notch-associated growth and the response to tumorigenesis (9). Furthermore, KDM5A can also interact with Sin3, thus resulting in de-acetylation, de-methylation, and nucleosome remodeling (10).

Disease Association

KDM5A is required for the drug-tolerant status of cancer cells (11).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Mus musculusNAEmbryonic Stem CellEmbryoGSE28343 ,GSM700784
Click  DownloadClick23093672

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K4me3 Homo sapiens H1 Embryonic Stem Cell Embryo GSE41009 ,GSM1006722 Bed     Big wiggle
Click   Download23382218
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
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282138 Bed     Big wiggle
Click   Download24495580
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282139 Bed     Big wiggle
Click   Download24495580
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282140 Bed     Big wiggle
Click   Download24495580
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 Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM605315 Bed     Big wiggle
Click   Download19829295
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE25533 ,GSM632035 Bed     Big wiggle
Click   Download22179133
H3K4me2 Homo sapiens H1 Embryonic Stem Cell Embryo GSE26320 ,GSM646343 Bed     Big wiggle
Click   Download21441907
H3K4me2 Homo sapiens H1 Embryonic Stem Cell Embryo GSE26320 ,GSM646344 Bed     Big wiggle
Click   Download21441907
H3K4me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE26136 ,GSM651193 Bed     Big wiggle
Click   Download21335234
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE33252 ,GSM686995 Bed     Big wiggle
Click   Download21655081
H3K4me2 Homo sapiens H1 Embryonic Stem Cell Embryo GSE29611 ,GSM733670 Bed     Big wiggle
Click   Download22955616
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE30203 ,GSM747544 Bed     Big wiggle
Click   Download22170606
H3K4me3 Mus musculus CMTi-1 Embryonic Stem Cell Embryo GSE34483 ,GSM849941 Bed     Big wiggle
Click   Download23260488
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881353 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881361 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881370 Bed     Big wiggle
Click   Download22682255
H3K4me3 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886518 Bed     Big wiggle
Click   Download24381111
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886531 Bed     Big wiggle
Click   Download24381111
H3K4me3 Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM906405 Bed     Big wiggle
Click   Download19829295
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. Fattaey, A.R., Helin, K., Dembski, M.S., Dyson, N., Harlow, E., Vuocolo, G.A., Hanobik, M.G., Haskell, K.M., Oliff, A., Defeo-Jones, D. et al. (1993) Characterization of the retinoblastoma binding proteins RBP1 and RBP2. Oncogene, 8, 3149-3156.
2. Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E. and Helin, K. (2007) RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell, 128, 1063-1076.
3. Tu, S., Teng, Y.C., Yuan, C., Wu, Y.T., Chan, M.Y., Cheng, A.N., Lin, P.H., Juan, L.J. and Tsai, M.D. (2008) The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC motif. Nat Struct Mol Biol, 15, 419-421.
4. Lopez-Bigas, N., Kisiel, T.A., Dewaal, D.C., Holmes, K.B., Volkert, T.L., Gupta, S., Love, J., Murray, H.L., Young, R.A. and Benevolenskaya, E.V. (2008) Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation. Mol Cell, 31, 520-530.
5. Klose, R.J., Yan, Q., Tothova, Z., Yamane, K., Erdjument-Bromage, H., Tempst, P., Gilliland, D.G., Zhang, Y. and Kaelin, W.G. (2007) The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell, 128, 889-900.
6. Benevolenskaya, E.V., Murray, H.L., Branton, P., Young, R.A. and Kaelin, W.G. (2005) Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Mol Cell, 18, 623-635.
7. Pasini, D., Hansen, K.H., Christensen, J., Agger, K., Cloos, P.A.C. and Helin, K. (2008) Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2. Gene Dev, 22, 1345-1355.
8. Stratmann, A. and Haendler, B. (2011) The histone demethylase JARID1A regulates progesterone receptor expression. Febs J, 278, 1458-1469.
9. Liefke, R., Oswald, F., Alvarado, C., Ferres-Marco, D., Mittler, G., Rodriguez, P., Dominguez, M. and Borggrefe, T. (2010) Histone demethylase KDM5A is an integral part of the core Notch-RBP-J repressor complex. Gene Dev, 24, 590-601.
10. van Oevelen, C., Wang, J.H., Asp, P., Yan, Q., Kaelin, W.G., Kluger, Y. and Dynlacht, B.D. (2008) A Role for Mammalian Sin3 in Permanent Gene Silencing. Mol Cell, 32, 359-370.
11. Sharma, S.V., Lee, D.Y., Li, B.H., Quinlan, M.P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M.A. et al. (2010) A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations. Cell, 141, 69-80.

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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