CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

KDM1AAOF2; KDM1; LSD1; BHC110

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K4me1;H3K9me2;H3K9me1;H3K4me2

Introduction

Full name: Lysine (K)-specific demethylase 1A . KDM1A is the first known histone demethylase. It forms one subunit of the CoREST-CtBP co-repressor complex and regulates gene transcription via both activation and repression through its demethylation function, which involves flavin-catalyzed oxidation (1-3). KDM1A can demethylate not only mono- and dimethylation of histone H3K4, but also mono- and dimethylation of histone H3K9 (1-2).

Function and Interaction

KDM1A is an important regulator of cell differentiation and development as well as tumorigenesis. KDM1A is recruited by Snail1 (which plays an essential role in the epithelial-mesenchymal transition) to the promoter of its target genes, leading to demethylation, reducing the degree of dimethylation on histone H3K4. Moreover, Snail1 performs its transcriptional repression function through KDM1A (4). KDM1A was recently found to be required for the repression of some genes related to human embryonic stem cell development containing bivalent marks (H3K4 and H3K27) (5). Additionally, KDM1A can interact with the androgen receptor, thus regulating transcription that is dependent on this receptor (2). KDM1A interacts with HDAC1, HDAC2, and CoREST, thus participating in gene modulation and chromatin modification (6-7). KDM1A also interacts with Snail1 (4).

Disease Association

KDM1A is downregulated in breast cancers and can decrease the invasion of breast cancer cells (8). KDM1A has also been shown to be overexpressed in bladder, colorectal, gastric, lung, and neuroendocrine cancers, chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma, suggesting it as a potential target in pharmaceutical treatments (9-14).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapiensSH-SY5YNeuronBone MarrowGSE58258 ,GSM1542271
Click  DownloadClick25684206

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K4me1 Mus musculus MEL Erythroid Progenitor Cell Blood GSE49847 ,GSM1000073 Bed     Big wiggle
Click   Download25409824
H3K9me2 Mus musculus 3T3-L1 Preadipocyte Adipose GSE41457 ,GSM1017632 Bed     Big wiggle
Click   Download23178591
H3K9me2 Mus musculus NA Embryonic Stem Cell Embryo GSE43231 ,GSM1059002 Bed     Big wiggle
Click   Download24361252
H3K4me1 Mus musculus C2C12 Myoblast Muscle GSE37184 ,GSM1101725 Bed     Big wiggle
Click   Download23651858
H3K4me1 Mus musculus C2C12 Myoblast Muscle GSE37184 ,GSM1101726 Bed     Big wiggle
Click   Download23651858
H3K4me1 Homo sapiens HeLa-S3 Epithelium Cervix GSE45489 ,GSM1104354 Bed     Big wiggle
Click   Download23592795
H3K4me1 Homo sapiens LNCaP Epithelium Prostate GSE47120 ,GSM1145323 Bed     Big wiggle
Click   Download23817021
H3K4me1 Mus musculus NA Embryonic Stem Cell Embryo GSE47950 ,GSM1163084 Bed     Big wiggle
Click   Download22981692
H3K4me1 Mus musculus NA Embryonic Stem Cell Embryo GSE47950 ,GSM1163085 Bed     Big wiggle
Click   Download22981692
H3K4me1 Mus musculus NA Embryonic Stem Cell Embryo GSE47950 ,GSM1163086 Bed     Big wiggle
Click   Download22981692
H3K4me1 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282133 Bed     Big wiggle
Click   Download24495580
H3K4me1 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282134 Bed     Big wiggle
Click   Download24495580
H3K4me1 Mus musculus R1 Embryonic Stem Cell Embryo GSE53087 ,GSM1282147 Bed     Big wiggle
Click   Download24495580
H3K4me1 Mus musculus J1 Embryonic Stem Cell Embryo GSE47085 ,GSM1359829 Bed     Big wiggle
Click   Download25564442
H3K4me1 Mus musculus J1 Embryonic Stem Cell Embryo GSE47085 ,GSM1359830 Bed     Big wiggle
Click   Download25564442
H3K4me1 Mus musculus J1 Embryonic Stem Cell Embryo GSE47085 ,GSM1359842 Bed     Big wiggle
Click   Download25564442
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE56872 ,GSM1370471 Bed     Big wiggle
Click   Download24857652
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE56872 ,GSM1370472 Bed     Big wiggle
Click   Download24857652
H3K4me2 Mus musculus 3T3-L1 Preadipocyte Adipose GSE56872 ,GSM1370473 Bed     Big wiggle
Click   Download24857652
H3K4me2 Mus musculus 3T3-L1 Preadipocyte Adipose GSE56872 ,GSM1370474 Bed     Big wiggle
Click   Download24857652
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE58491 ,GSM1412497 Bed     Big wiggle
Click   Download25503565
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE58491 ,GSM1412506 Bed     Big wiggle
Click   Download25503565
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE58491 ,GSM1412515 Bed     Big wiggle
Click   Download25503565
H3K4me1 Homo sapiens None Fibroblast None GSE53837 ,GSM1435528 Bed     Big wiggle
Click   Download25326100
H3K4me1 Homo sapiens GM2555 Fibroblast None GSE53837 ,GSM1435530 Bed     Big wiggle
Click   Download25326100
H3K4me1 Homo sapiens LNCaP Epithelium Prostate GSE62492 ,GSM1527828 Bed     Big wiggle
Click   Download25537508
H3K4me1 Homo sapiens LNCaP Epithelium Prostate GSE62492 ,GSM1527829 Bed     Big wiggle
Click   Download25537508
H3K4me1 Homo sapiens SH-SY5Y Neuron Bone Marrow GSE62726 ,GSM1532409 Bed     Big wiggle
Click   Download25416950
H3K4me1 Mus musculus None Cortical Neuron Neuric GSE63271 ,GSM1544909 Bed     Big wiggle
Click   Download26214369
H3K4me1 Mus musculus None Cortical Neuron Neuric GSE63271 ,GSM1544911 Bed     Big wiggle
Click   Download26214369
H3K4me2 Homo sapiens NCI-H526 Epithelium Lung GSE66298 ,GSM1619042 Bed     Big wiggle
Click   Download26175415
H3K4me1 Homo sapiens NCI-H526 Epithelium Lung GSE66298 ,GSM1619043 Bed     Big wiggle
Click   Download26175415
H3K4me1 Homo sapiens K562 Erythroblast Bone Marrow GSE70482 ,GSM1782706 Bed     Big wiggle
Click   Download26280331
H3K4me1 Homo sapiens K562 Erythroblast Bone Marrow GSE70482 ,GSM1782707 Bed     Big wiggle
Click   Download26280331
H3K4me2 Homo sapiens None Fibroblast None GSE71033 ,GSM1825749 Bed     Big wiggle
Click   Download26186193
H3K4me2 Mus musculus 3T3-L1 Preadipocyte Adipose GSE21365 ,GSM535742 Bed     Big wiggle
Click   Download20887899
H3K4me1 Mus musculus 3T3-L1 Preadipocyte Adipose GSE21365 ,GSM535743 Bed     Big wiggle
Click   Download20887899
H3K4me1 Homo sapiens K562 Erythroblast Bone Marrow GSE24779 ,GSM610339 Bed     Big wiggle
Click   Download20959602
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE25533 ,GSM632035 Bed     Big wiggle
Click   Download22179133
H3K4me2 Homo sapiens K562 Erythroblast Bone Marrow GSE26320 ,GSM646442 Bed     Big wiggle
Click   Download21441907
H3K4me2 Homo sapiens K562 Erythroblast Bone Marrow GSE26320 ,GSM646443 Bed     Big wiggle
Click   Download21441907
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE33252 ,GSM686995 Bed     Big wiggle
Click   Download21655081
H3K4me1 Mus musculus ZhBTc4 Embryonic Stem Cell Embryo GSE27844 ,GSM687286 Bed     Big wiggle
Click   Download22297846
H3K4me1 Mus musculus ZhBTc4 Embryonic Stem Cell Embryo GSE27844 ,GSM687287 Bed     Big wiggle
Click   Download22297846
H3K4me1 Mus musculus ZhBTc4 Embryonic Stem Cell Embryo GSE27844 ,GSM687288 Bed     Big wiggle
Click   Download22297846
H3K4me2 Mus musculus C2C12 Myoblast Muscle GSE25308 ,GSM721290 Bed     Big wiggle
Click   Download21551099
H3K4me2 Mus musculus C2C12 Myoblast Muscle GSE25308 ,GSM721291 Bed     Big wiggle
Click   Download21551099
H3K4me2 Homo sapiens K562 Erythroblast Bone Marrow GSE29611 ,GSM733651 Bed     Big wiggle
Click   Download22955616
H3K4me1 Homo sapiens K562 Erythroblast Bone Marrow GSE29611 ,GSM733692 Bed     Big wiggle
Click   Download22955616
H3K4me2 Homo sapiens HeLa-S3 Epithelium Cervix GSE29611 ,GSM733734 Bed     Big wiggle
Click   Download22955616
H3K4me2 Mus musculus NA Embryonic Stem Cell Embryo GSE30203 ,GSM747544 Bed     Big wiggle
Click   Download22170606
H3K4me1 Homo sapiens K562 Erythroblast Bone Marrow GSE31755 ,GSM788085 Bed     Big wiggle
Click   Download25409831
H3K4me1 Homo sapiens HeLa-S3 Epithelium Cervix GSE29611 ,GSM798322 Bed     Big wiggle
Click   Download22955616
H3K4me1 Mus musculus C2C12 Myoblast Muscle GSE33227 ,GSM822512 Bed     Big wiggle
Click   Download24714595
H3K4me1 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE27844 ,GSM845238 Bed     Big wiggle
Click   Download22297846
H3K4me1 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE27844 ,GSM845239 Bed     Big wiggle
Click   Download22297846
H3K4me1 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE27844 ,GSM845242 Bed     Big wiggle
Click   Download22297846
H3K4me1 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE27844 ,GSM845243 Bed     Big wiggle
Click   Download22297846
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881353 Bed     Big wiggle
Click   Download22682255
H3K4me1 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881360 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881361 Bed     Big wiggle
Click   Download22682255
H3K4me1 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881369 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus E14 Embryonic Stem Cell Embryo GSE38596 ,GSM881370 Bed     Big wiggle
Click   Download22682255
H3K4me2 Mus musculus R1 Embryonic Stem Cell Embryo GSE36294 ,GSM886531 Bed     Big wiggle
Click   Download24381111
H3K4me1 Homo sapiens None Keratinocyte Foreskin GSE16368 ,GSM941736 Bed     Big wiggle
Click   Download20944595
H3K4me1 Homo sapiens None Keratinocyte Foreskin GSE16368 ,GSM958161 Bed     Big wiggle
Click   Download20944595
H3K4me1 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970225 Bed     Big wiggle
Click   Download24289921
H3K4me1 Mus musculus E36 Embryonic Stem Cell Embryo GSE39496 ,GSM970226 Bed     Big wiggle
Click   Download24289921
H3K4me1 Mus musculus NA Granulocytic Progenitor Cell Bone Marrow GSE40440 ,GSM994230 Bed     Big wiggle
Click   Download23795291
H3K4me1 Mus musculus NA Granulocytic Progenitor Cell Bone Marrow GSE40440 ,GSM994231 Bed     Big wiggle
Click   Download23795291

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. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A. and Casero, R.A. (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119, 941-953.
2. Metzger, E., Wissmann, M., Yin, N., Muller, J.M., Schneider, R., Peters, A.H.F.M., Gunther, T., Buettner, R. and Schule, R. (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature, 437, 436-439.
3. Forneris, F., Binda, C., Vanoni, M.A., Mattevi, A. and Battaglioli, E. (2005) Histone demethylation catalysed by LSD1 is a flavin-dependent oxidative process. Febs Lett, 579, 2203-2207.
4. Lin, T., Ponn, A., Hu, X., Law, B.K. and Lu, J. (2010) Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene, 29, 4896-4904.
5. Adamo, A., Sese, B., Boue, S., Castano, J., Paramonov, I., Barrero, M.J. and Belmonte, J.C.I. (2011) LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat Cell Biol, 13, 652-U265.
6. Forneris, F., Binda, C., Battaglioli, E. and Mattevi, A. (2008) LSD1: oxidative chemistry for multifaceted functions in chromatin regulation. Trends Biochem Sci, 33, 181-189.
7. Mosammaparast, N. and Shi, Y. (2010) Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases. Annual Review of Biochemistry, Vol 79, 79, 155-179.
8. Wang, Y., Zhang, H., Chen, Y.P., Sun, Y.M., Yang, F., Yu, W.H., Liang, J., Sun, L.Y., Yang, X.H., Shi, L. et al. (2009) LSD1 Is a Subunit of the NuRD Complex and Targets the Metastasis Programs in Breast Cancer. Cell, 138, 660-672.
9. Hayami, S., Kelly, J.D., Cho, H.S., Yoshimatsu, M., Unoki, M., Tsunoda, T., Field, H.I., Neal, D.E., Yamaue, H., Ponder, B.A.J. et al. (2011) Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer, 128, 574-586.
10. Bennani-Baiti, I.M., Machado, I., Llombart-Bosch, A. and Kovar, H. (2012) Lysine-specific demethylase 1 (LSD1/KDM1A/AOF2/BHC110) is expressed and is an epigenetic drug target in chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Hum Pathol, 43, 1300-1307.
11. Huang, J., Sengupta, R., Espejo, A.B., Lee, M.G., Dorsey, J.A., Richter, M., Opravil, S., Shiekhattar, R., Bedford, M.T., Jenuwein, T. et al. (2007) p53 is regulated by the lysine demethylase LSD1. Nature, 449, 105-U180.
12. Lim, S., Janzer, A., Becker, A., Zimmer, A., Schule, R., Buettner, R. and Kirfel, J. (2010) Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis, 31, 512-520.
13. Magerl, C., Ellinger, J., Braunschweig, T., Kremmer, E., Koch, L.K., Holler, T., Buttner, R., Luscher, B. and Gutgemann, I. (2010) H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1. Hum Pathol, 41, 181-189.
14. Schulte, J.H., Lim, S.Y., Schramm, A., Friedrichs, N., Koster, J., Versteeg, R., Ora, I., Pajtler, K., Klein-Hitpass, L., Kuhfittig-Kulle, S. et al. (2009) Lysine-Specific Demethylase 1 Is Strongly Expressed in Poorly Differentiated Neuroblastoma: Implications for Therapy. Cancer Res, 69, 2065-2071.

Figure Gallery

pix pix pix pix pix pix

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.

Contact

houshuang [at] tongji dot edu dot cn