histone demethylases


Summary: Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.

Top Publications

  1. Li F, Zheng L, Chen X, Zhao X, Briggs S, Du H. Gcn5-mediated Rph1 acetylation regulates its autophagic degradation under DNA damage stress. Nucleic Acids Res. 2017;45:5183-5197 pubmed publisher
    ..Our findings may provide a general connection between DNA damage, protein acetylation and autophagy. ..
  2. Mould D, Bremberg U, Jordan A, Geitmann M, Maiques Diaz A, McGonagle A, et al. Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1. Bioorg Med Chem Lett. 2017;27:3190-3195 pubmed publisher
    ..Compound 11p was found to have moderate oral bioavailability in mice suggesting its potential for use as an in vivo tool compound. ..
  3. Ding L, Wang Z, Sun X, Yang J, Ma C, Li W, et al. 3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors. Bioorg Med Chem Lett. 2017;27:3521-3528 pubmed publisher
    ..Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. ..
  4. Takagi S, Ishikawa Y, Mizutani A, Iwasaki S, Matsumoto S, Kamada Y, et al. LSD1 Inhibitor T-3775440 Inhibits SCLC Cell Proliferation by Disrupting LSD1 Interactions with SNAG Domain Proteins INSM1 and GFI1B. Cancer Res. 2017;77:4652-4662 pubmed publisher
    ..Targeting these critical interactions with LSD1 inhibitors offers a novel rational strategy to therapeutically manage SCLC. Cancer Res; 77(17); 4652-62. ©2017 AACR. ..
  5. Maina P, Shao P, Jia X, Liu Q, Umesalma S, Marin M, et al. Histone demethylase PHF8 regulates hypoxia signaling through HIF1? and H3K4me3. Biochim Biophys Acta Gene Regul Mech. 2017;1860:1002-1012 pubmed publisher
    ..However, how histone demethylases regulate hypoxia signaling is not fully understood...
  6. Borrello M, Schinor B, Bartels K, Benelkebir H, Pereira S, Al Jamal W, et al. Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A). Bioorg Med Chem Lett. 2017;27:2099-2101 pubmed publisher
    ..In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement. ..
  7. Petruk S, Cai J, Sussman R, Sun G, Kovermann S, Mariani S, et al. Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation. Mol Cell. 2017;66:247-257.e5 pubmed publisher
    ..This insight may explain the developmental plasticity of stem cells and facilitate their exploitation for therapeutic purposes. ..
  8. Wesche J, Kuhn S, Kessler B, Salton M, Wolf A. Protein arginine methylation: a prominent modification and its demethylation. Cell Mol Life Sci. 2017;74:3305-3315 pubmed publisher
  9. Gianoglio S, Moglia A, Acquadro A, Comino C, Portis E. The genome-wide identification and transcriptional levels of DNA methyltransferases and demethylases in globe artichoke. PLoS ONE. 2017;12:e0181669 pubmed publisher

More Information


  1. El Mansouri F, Nebbaki S, Kapoor M, Afif H, Martel Pelletier J, Pelletier J, et al. Lysine-specific demethylase 1-mediated demethylation of histone H3 lysine 9 contributes to interleukin 1?-induced microsomal prostaglandin E synthase 1 expression in human osteoarthritic chondrocytes. Arthritis Res Ther. 2014;16:R113 pubmed publisher
  2. Dhall A, Weller C, Chu A, Shelton P, Chatterjee C. Chemically Sumoylated Histone H4 Stimulates Intranucleosomal Demethylation by the LSD1-CoREST Complex. ACS Chem Biol. 2017;12:2275-2280 pubmed publisher
    ..Thus, we have identified histone modification by SUMO as the first PTM that stimulates intranucleosomal demethylation by the developmentally critical LSD1-CoREST complex. ..
  3. Shackleton M. Moving targets that drive cancer progression. N Engl J Med. 2010;363:885-6 pubmed publisher
  4. Jia G, Wang W, Li H, Mao Z, Cai G, Sun J, et al. A systematic evaluation of the compatibility of histones containing methyl-lysine analogues with biochemical reactions. Cell Res. 2009;19:1217-20 pubmed publisher
  5. Hurst C, Alder O, Platt F, Droop A, Stead L, Burns J, et al. Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency. Cancer Cell. 2017;32:701-715.e7 pubmed publisher
    ..More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males. ..
  6. Speranzini V, Ciossani G, Marabelli C, Mattevi A. Probing the interaction of the p53 C-terminal domain to the histone demethylase LSD1. Arch Biochem Biophys. 2017;632:202-208 pubmed publisher
    ..We conclude that p53-CTD inhibits LSD1 activity and that the direct association between the two proteins can contribute to their functional cross-talk. ..
  7. Rodríguez Hernández G, Hauer J, Martín Lorenzo A, Schäfer D, Bartenhagen C, García Ramírez I, et al. Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases. Cancer Res. 2017;77:4365-4377 pubmed publisher
    ..i>Cancer Res; 77(16); 4365-77. ©2017 AACR. ..
  8. Mould D, Alli C, Bremberg U, Cartic S, Jordan A, Geitmann M, et al. Development of (4-Cyanophenyl)glycine Derivatives as Reversible Inhibitors of Lysine Specific Demethylase 1. J Med Chem. 2017;60:7984-7999 pubmed publisher
    ..67 ?M in a surrogate cellular biomarker assay. Moreover, this derivative does not display the same level of hERG liability as observed with 1 and represents a promising lead for further development...
  9. Zhou Z, Zhang H, Liu Y, Zhang Z, Du G, Li H, et al. Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin. J Cell Physiol. 2018;233:1359-1369 pubmed publisher
    ..These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression. ..
  10. Soto D, Barton C, Munger K, McLaughlin Drubin M. KDM6A addiction of cervical carcinoma cell lines is triggered by E7 and mediated by p21CIP1 suppression of replication stress. PLoS Pathog. 2017;13:e1006661 pubmed publisher
    ..Therefore, KDM6A and p21CIP1 expression are essential to curb E7 induced replication stress to levels that do not markedly interfere with cell viability...
  11. Zhou J, Wang F, Xu C, Zhou Z, Zhang W. The histone demethylase JMJD2A regulates the expression of BDNF and mediates neuropathic pain in mice. Exp Cell Res. 2017;361:155-162 pubmed publisher
    ..Taken together, our findings demonstrate that up-regulation of JMJD2A promotes neuropathic pain and it may serve as a promising target for treatment of chronic neuropathic pain...
  12. Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, et al. A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia. 2017;31:2303-2314 pubmed publisher
  13. Fang R, Xu J, Lin H, Xu X, Tian F. The histone demethylase lysine-specific demethylase-1-mediated epigenetic silence of KLF2 contributes to gastric cancer cell proliferation, migration, and invasion. Tumour Biol. 2017;39:1010428317698356 pubmed publisher
  14. Castex J, Willmann D, Kanouni T, Arrigoni L, Li Y, Friedrich M, et al. Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Dis. 2017;8:e2631 pubmed publisher
    ..In conclusion, by repression of Sirt4, Lsd1 directs the epigenetic control of TSC immortality via maintenance of metabolic flexibility. ..
  15. Niebel D, Kirfel J, Janzen V, Höller T, Majores M, Gütgemann I. Lysine-specific demethylase 1 (LSD1) in hematopoietic and lymphoid neoplasms. Blood. 2014;124:151-2 pubmed publisher
  16. Tang J, Xie Y, Xu X, Yin Y, Jiang R, Deng L, et al. Bidirectional transcription of Linc00441 and RB1 via H3K27 modification-dependent way promotes hepatocellular carcinoma. Cell Death Dis. 2017;8:e2675 pubmed publisher
  17. Schmidt O, Weyer Y, Fink M, Muller M, Weys S, Bindreither M, et al. Regulation of Rab5 isoforms by transcriptional and post-transcriptional mechanisms in yeast. FEBS Lett. 2017;591:2803-2815 pubmed publisher
    ..Once this regulation is bypassed, Ypt53 protein levels surpass Vps21, and Ypt53 is sufficient to maintain endosomal function and cell growth. ..
  18. Zheng Y, Chang J, Zhang T, Suo F, Chen X, Liu Y, et al. An Overview on Screening Methods for Lysine Specific Demethylase 1 (LSD1) Inhibitors. Curr Med Chem. 2017;24:2496-2504 pubmed publisher
    ..Each of them has distinct advantages and disadvantages, and none of these methods is perfect. In order to exclude the false positive results, at least one additional method should be applied to screen LSD1 inhibitors. ..
  19. Liang Y, Ahmed M, Guo H, Soares F, Hua J, Gao S, et al. LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression. Cancer Res. 2017;77:5479-5490 pubmed publisher
    ..Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease. Cancer Res; 77(20); 5479-90. ©2017 AACR. ..
  20. Xie G, Liu X, Zhang Y, Li W, Liu S, Chen Z, et al. UTX promotes hormonally responsive breast carcinogenesis through feed-forward transcription regulation with estrogen receptor. Oncogene. 2017;36:5497-5511 pubmed publisher
  21. Cui Y, Cui C, Yang Z, Ni W, Jin Y, Xuan Y. Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma. Exp Mol Pathol. 2017;102:347-353 pubmed publisher
    ..026). Our results suggest that Gli1 may be a potential LSCC stem cell marker and an independent indicator of poor prognosis for patients with LSCC. ..
  22. Kouzarides T. SnapShot: Histone-modifying enzymes. Cell. 2007;128:802 pubmed
  23. Yang J, Milasta S, Hu D, AlTahan A, Interiano R, Zhou J, et al. Targeting Histone Demethylases in MYC-Driven Neuroblastomas with Ciclopirox. Cancer Res. 2017;77:4626-4638 pubmed publisher
    ..Here we show that multiple histone demethylases influence the viability and poor prognosis of neuroblastoma cells, where MYC is often overexpressed...
  24. Wang S, Tang Z, Chen C, Shimada M, Koche R, Wang L, et al. A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription. Mol Cell. 2017;67:308-321.e6 pubmed publisher
  25. Suzuki T, Miyata N. Lysine demethylases inhibitors. J Med Chem. 2011;54:8236-50 pubmed publisher
  26. Myrick D, Christopher M, Scott A, Simon A, Donlin Asp P, Kelly W, et al. KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice. PLoS ONE. 2017;12:e0177473 pubmed publisher
    ..Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse. ..
  27. Kaiser J. Genes link epigenetics and cancer. Science. 2010;330:577 pubmed publisher
  28. Shortt J, Ott C, Johnstone R, Bradner J. A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 2017;17:160-183 pubmed publisher
    ..By annotating these reagents, we aim to share our perspectives on an informative 'epigenomic toolbox' of broad utility to the research community. ..
  29. Zhang Z, Lei A, Xu L, Chen L, Chen Y, Zhang X, et al. Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells. J Biol Chem. 2017;292:12842-12859 pubmed publisher
    ..This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells. ..
  30. Saha D, Singh A, Hussain T, Srivastava V, Sengupta S, Kar A, et al. Epigenetic suppression of human telomerase (hTERT) is mediated by the metastasis suppressor NME2 in a G-quadruplex-dependent fashion. J Biol Chem. 2017;292:15205-15215 pubmed publisher
    ..Together, our results support a mechanism of hTERT epigenetic control involving a G-quadruplex promoter motif, which potentially can be targeted by tailored small molecules. ..
  31. Ambrosio S, Saccà C, Majello B. Epigenetic regulation of epithelial to mesenchymal transition by the Lysine-specific demethylase LSD1/KDM1A. Biochim Biophys Acta Gene Regul Mech. 2017;1860:905-910 pubmed publisher
    ..Here we present an overview of the role of LSD1 in the EMT process, summarizing recent findings on its emerging functions in cell migration and invasion in cancer. ..
  32. Ma J, Song S, Guo M, Zhou J, Liu F, Peng L, et al. Long-term exposure to PM2.5 lowers influenza virus resistance via down-regulating pulmonary macrophage Kdm6a and mediates histones modification in IL-6 and IFN-? promoter regions. Biochem Biophys Res Commun. 2017;493:1122-1128 pubmed publisher
    ..5 and a resultant increase in H3K4 and H3K9 methylation in IL-6 and IFN-? promoter regions. In summary, PM2.5 causes injuries of lung tissue cells and downregulates immune defense mechanisms in the lung. ..
  33. Alamdar A, Xi G, Huang Q, Tian M, Eqani S, Shen H. Arsenic activates the expression of 3?-HSD in mouse Leydig cells through repression of histone H3K9 methylation. Toxicol Appl Pharmacol. 2017;326:7-14 pubmed publisher
    ..Considering these results, we conclude that arsenic exposure induced 3?-HSD up-regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1 cells. ..
  34. Ishiguro K, Watanabe O, Nakamura M, Yamamura T, Matsushita M, Goto H, et al. Inhibition of KDM4A activity as a strategy to suppress interleukin-6 production and attenuate colitis induction. Clin Immunol. 2017;180:120-127 pubmed publisher
    ..The KDM4A inhibitor ML324 showed similar actions on IL-6 production and colitis induction. We propose the inhibition of KDM4A activity as a strategy to suppress IL-6 production and attenuate colitis induction. ..
  35. Dorosz J, Olsen L, Seger S, Steinhauer C, Bouras G, Helgstrand C, et al. Structure-Based Design of a New Scaffold for Cell-Penetrating Peptidic Inhibitors of the Histone Demethylase PHF8. Chembiochem. 2017;18:1369-1375 pubmed publisher
    ..The cyclic peptide's ability to penetrate cells is achieved by incorporation of a sequence derived from HIV Tat. The derived cyclic peptide can be used as a starting compound in the search for potent and selective PHF8 inhibitors. ..
  36. Byun S, Kim Y, Zhang Y, Kong B, Guo G, Sadoshima J, et al. A postprandial FGF19-SHP-LSD1 regulatory axis mediates epigenetic repression of hepatic autophagy. EMBO J. 2017;36:1755-1769 pubmed publisher
    ..This study demonstrates that the FGF19-SHP-LSD1 axis maintains homeostasis by suppressing unnecessary autophagic breakdown of cellular components, including lipids, under nutrient-rich postprandial conditions. ..
  37. Xi J, Xu S, Wu L, Ma T, Liu R, Liu Y, et al. Design, synthesis and biological activity of 3-oxoamino-benzenesulfonamides as selective and reversible LSD1 inhibitors. Bioorg Chem. 2017;72:182-189 pubmed publisher
    ..Taken together, 3-oxoamino-benzenesulfonamides may represent a new class of reversible LSD1 inhibitors and 7b and 7h were two hit compounds deserved further structural optimization. ..
  38. Xun J, Wang D, Shen L, Gong J, Gao R, Du L, et al. JMJD3 suppresses stem cell-like characteristics in breast cancer cells by downregulation of Oct4 independently of its demethylase activity. Oncotarget. 2017;8:21918-21929 pubmed publisher
    ..Administration of paricalcitol leads to upregulation of JMJD3 that suppresses Oct4 expression and the stem cell-like characteristics in breast cancer. ..
  39. Acquaviva C, Gelsi Boyer V, Birnbaum D. Myelodysplastic syndromes: lost between two states?. Leukemia. 2010;24:1-5 pubmed publisher
  40. Zhou B, Yang X, Jiang J, Wang Y, Li M, Li M, et al. Silkworm (Bombyx mori) BmLid is a histone lysine demethylase with a broader specificity than its homolog in Drosophila and mammals. Cell Res. 2010;20:1079-82 pubmed publisher
  41. Mould D, Bremberg U, Jordan A, Geitmann M, McGonagle A, Somervaille T, et al. Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1. Bioorg Med Chem Lett. 2017;27:4755-4759 pubmed publisher
    ..This work further demonstrates the versatility of scaffold-hopping asa method to develop structurally diverse, potent inhibitors of LSD1. ..
  42. Terashima M, Ishimura A, Wanna Udom S, Suzuki T. Epigenetic regulation of epithelial-mesenchymal transition by KDM6A histone demethylase in lung cancer cells. Biochem Biophys Res Commun. 2017;490:1407-1413 pubmed publisher
    ..This study demonstrated a novel regulatory role of KDM6A histone demethylase in the epigenetic control of EMT process in lung cancer cells. ..
  43. Yan N, Xu L, Wu X, Zhang L, Fei X, Cao Y, et al. GSKJ4, an H3K27me3 demethylase inhibitor, effectively suppresses the breast cancer stem cells. Exp Cell Res. 2017;359:405-414 pubmed publisher
    ..Collectively, our results provide strong supports that H3K27me3 exerts a suppressive influence on BCSCs and reveal that GSKJ4 is capable to be a prospective agent targeting BCSCs. ..
  44. Lee J, Park J, Choi H, Won H, Joo H, Shin D, et al. LSD1 demethylates HIF1α to inhibit hydroxylation and ubiquitin-mediated degradation in tumor angiogenesis. Oncogene. 2017;36:5512-5521 pubmed publisher
    ..Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation. ..
  45. Colmenares S, Swenson J, Langley S, Kennedy C, Costes S, Karpen G. Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity. Dev Cell. 2017;42:156-169.e5 pubmed publisher
    ..We conclude that dKDM4A, in addition to its previously characterized role in euchromatin, utilizes both enzymatic and structural mechanisms to regulate heterochromatin organization and functions. ..
  46. Wu J, He Z, Yang X, Li K, Wang D, Sun F. RCCD1 depletion attenuates TGF-β-induced EMT and cell migration by stabilizing cytoskeletal microtubules in NSCLC cells. Cancer Lett. 2017;400:18-29 pubmed publisher
    ..Collectively, these findings support RCCD1 as a novel regulator of TGF-β-induced EMT in NSCLC. ..
  47. Sankar A, Kooistra S, Gonzalez J, Ohlsson C, Poutanen M, Helin K. Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development. Development. 2017;144:3264-3277 pubmed publisher
    ..Thus, our study dissects an important dual role for maternal Kdm4a in determining faithful early embryonic development and the implantation process. ..
  48. Bennani Baiti I. Integration of ER?-PELP1-HER2 signaling by LSD1 (KDM1A/AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer. Breast Cancer Res. 2012;14:112 pubmed publisher
    ..The relevance of PELP1-LSD1 signaling to other nuclear hormone receptor-dependent cancers and structural considerations for the selective drug targeting of LSD1 are further discussed in this editorial. ..
  49. Xu T, Park S, Giaimo B, Hall D, Ferrante F, Ho D, et al. RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. EMBO J. 2017;36:3232-3249 pubmed publisher
  50. Huang M, Hou J, Wang Y, Xie M, Wei C, Nie F, et al. Long Noncoding RNA LINC00673 Is Activated by SP1 and Exerts Oncogenic Properties by Interacting with LSD1 and EZH2 in Gastric Cancer. Mol Ther. 2017;25:1014-1026 pubmed publisher