CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

KDM5CMRXJ; SMCX; MRXSJ; XE169; MRXSCJ; JARID1C; DXS1272E

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K4me3;H3K4me2

Introduction

Full Name: Lysine (K)-specific demethylase 5C . KDM5C is a member of the highly conserved ARID protein family and was first recognized as an X-chromosome gene that escapes X-inactivation in both mice and humans. It contains a JmjN domain, an ARID domain, a JmjC domain, a C5HC2 zinc finger domain, and a PHD zinc finger domain. KDM5C expression may be tissue- and developmental stage-specific, and it is associated with transcriptional repression and chromatin remodeling, playing a role in normal brain development and function, tumorigenesis, development, cell growth, and differentiation (1-13).

Function and Interaction

KDM5C forms a complex with HDAC1, HDAC2, G9a, and REST. REST and KDM5C have been shown to co-bind the promoter regions of some REST target genes, indicating the involvement of KDM5C in chromatin dynamics and REST-related repression (2). KDM5C is also associated with Smad3, an intracellular mediator of transforming growth factor-β (TGF-β), and acting as a corepressor of Smad3. Hence, KDM5C may be involved in tumorigenesis via interfering with the tumor-suppressing activity of the TGF-b/ Smad3 signaling pathway (3).

Disease Association

Mutations in KDM5C are related to X-linked mental retardation (XLMR) and epilepsy (4-5). One study also associated a mutation in KDM5C with a patient with autism spectrum disorder (6). This novel mutation in KDM5C can result in intellectual disability, short stature, speech delay, hyperactivity, violent behavior, and a high palate (8). KDM5Cs are suggested to act as tumor enhancers in clear-cell renal cell carcinoma (ccRCC) (7).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapienscaki-1NoneKidneyGSE73267 ,GSM1889902
Click  DownloadClick26551685

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
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 caki-1 None Kidney GSE73267 ,GSM1889909 Bed     Big wiggle
Click   Download26551685
H3K4me3 Homo sapiens caki-1 None Kidney GSE73267 ,GSM1889910 Bed     Big wiggle
Click   Download26551685
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 K562 Erythroblast Bone Marrow GSE28162 ,GSM608165 Bed     Big wiggle
Click   Download21596310
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 Homo sapiens K562 Erythroblast Bone Marrow GSE35294 ,GSM865280 Bed     Big wiggle
Click   Download23754963
H3K4me3 Homo sapiens K562 Erythroblast Bone Marrow GSE35294 ,GSM865281 Bed     Big wiggle
Click   Download23754963
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. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M. and Shi, Y. (2007) The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell, 128, 1077-1088.
2. Tahiliani, M., Mei, P., Fang, R., Leonor, T., Rutenberg, M., Shimizu, F., Li, J., Rao, A. and Shi, Y. (2007) The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature, 447, 601-605.
3. Kim, T.D., Shin, S. and Janknecht, R. (2008) Repression of Smad3 activity by histone demethylase SMCX/JARID1C. Biochem Biophys Res Commun, 366, 563-567.
4. Jensen, L.R., Amende, M., Gurok, U., Moser, B., Gimmel, V., Tzschach, A., Janecke, A.R., Tariverdian, G., Chelly, J., Fryns, J.P. et al. (2005) Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am J Hum Genet, 76, 227-236.
5. Tzschach, A., Lenzner, S., Moser, B., Reinhardt, R., Chelly, J., Fryns, J.P., Kleefstra, T., Raynaud, M., Turner, G., Ropers, H.H. et al. (2006) Novel JARID1C/SMCX Mutations in Patients With Xlinked Mental Retardation. Hum Mutat, 27, 389-390.
6. Adegbola, A., Gao, H.L., Sommer, S. and Browning, M. (2008) A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). Am J Med Genet A, 146A, 505-511.
7. Niu, X., Zhang, T., Liao, L., Zhou, L., Lindner, D.J., Zhou, M., Rini, B., Yan, Q. and Yang, H. (2012) The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene, 31, 776-786.
8. Santos-Reboucas, C.B., Fintelman-Rodrigues, N., Jensen, L.R., Kuss, A.W., Ribeiro, M.G., Campos, M., Santos, J.M. and Pimentel, M.M.G. (2011) A novel nonsense mutation in KDM5C/JARID1C gene causing intellectual disability, short stature and speech delay. Neurosci Lett, 498, 67-71.
9. Yi, L., Hao, Z., Yang, T., Wang, S., Xing, B. and Xu, Y. (2007) cDNA cloning, bioinformatic and tissue-specific expression analysis of porcine JARID1C gene. J Genet Genomics, 34, 1088-1096.
10. Agulnik, A.I., Mitchell, M.J., Mattei, M.G., Borsani, G., Avner, P.A., Lerner, J.L. and Bishop, C.E. (1994) A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human. Hum Mol Genet, 3, 879-884.
11. Wu, J., Salido, E.C., Yen, P.H., Mohandas, T.K., Heng, H.H., Tsui, L.C., Park, J., Chapman, V.M. and Shapiro, L.J. (1994) The murine Xe169 gene escapes X-inactivation like its human homologue. Nat Genet, 7, 491-496.
12. Li, N. and Carrel, L. (2008) Escape from X chromosome inactivation is an intrinsic property of the Jarid1c locus. P Natl Acad Sci USA, 105, 17055-17060.
13. Xu, J., Deng, X.X. and Disteche, C.M. (2008) Sex-Specific Expression of the X-Linked Histone Demethylase Gene Jarid1c in Brain. PLoS One, 3.

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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