Kdm6a

Summary

Gene Symbol: Kdm6a
Description: lysine (K)-specific demethylase 6A
Alias: Utx, lysine-specific demethylase 6A, histone demethylase UTX, ubiquitously transcribed TPR protein on the X chromosome, ubiquitously transcribed X chromosome tetratricopeptide repeat protein, ubiquitously transcribed tetratricopeptide repeat gene, X chromosome
Species: mouse
Products:     Kdm6a

Top Publications

  1. Grbavec D, Lo R, Liu Y, Greenfield A, Stifani S. Groucho/transducin-like enhancer of split (TLE) family members interact with the yeast transcriptional co-repressor SSN6 and mammalian SSN6-related proteins: implications for evolutionary conservation of transcription repression mechanisms. Biochem J. 1999;337 ( Pt 1):13-7 pubmed
    ..These findings suggest that mammalian TLE and UTY/X proteins may mediate repression mechanisms similar to those performed by TUP1-SSN6 in yeast. ..
  2. Morales Torres C, Laugesen A, Helin K. Utx is required for proper induction of ectoderm and mesoderm during differentiation of embryonic stem cells. PLoS ONE. 2013;8:e60020 pubmed publisher
    ..Demethylation of H3K27me3 by the histone demethylases Utx and Jmjd3 is important for the activation of lineage choice genes in response to developmental signals...
  3. Hong S, Cho Y, Yu L, Yu H, Veenstra T, Ge K. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc Natl Acad Sci U S A. 2007;104:18439-44 pubmed
    ..Here we show the JmjC domain-containing protein UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), as well as the related JMJD3 (jumonji domain ..
  4. Xu J, Deng X, Watkins R, Disteche C. Sex-specific differences in expression of histone demethylases Utx and Uty in mouse brain and neurons. J Neurosci. 2008;28:4521-7 pubmed publisher
    ..b>Utx (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome) is an escapee gene that encodes a ..
  5. Wang A, Zare H, Mousavi K, Wang C, Moravec C, Sirotkin H, et al. The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis. EMBO J. 2013;32:1075-86 pubmed publisher
    ..By regulating proper engagement and function of the H3K27 demethylase KDM6A (UTX), Spt6 effectively promotes H3K27 demethylation, muscle gene expression, and cell differentiation...
  6. Shpargel K, Sengoku T, Yokoyama S, Magnuson T. UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet. 2012;8:e1002964 pubmed publisher
    UTX (KDM6A) and UTY are homologous X and Y chromosome members of the Histone H3 Lysine 27 (H3K27) demethylase gene family...
  7. Wang C, Lee J, Cho Y, Xiao Y, Jin Q, Liu C, et al. UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity. Proc Natl Acad Sci U S A. 2012;109:15324-9 pubmed
    To investigate the role of histone H3K27 demethylase UTX in embryonic stem (ES) cell differentiation, we have generated UTX knockout (KO) and enzyme-dead knock-in male ES cells...
  8. Welstead G, Creyghton M, Bilodeau S, Cheng A, Markoulaki S, Young R, et al. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc Natl Acad Sci U S A. 2012;109:13004-9 pubmed publisher
    ..It has been suggested that the recently discovered class of histone demethylases (UTX and JMJD3) that specifically target the repressive H3K27me3 modification play an important role in the activation ..
  9. Miller S, Mohn S, Weinmann A. Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Mol Cell. 2010;40:594-605 pubmed publisher
    ..In this study, we show that the H3K27 demethylases, Jmjd3 and UTX, mediate a functional interaction between the lineage-defining T-box transcription factor family and a Brg1-..

More Information

Publications54

  1. Greenfield A, Carrel L, Pennisi D, Philippe C, Quaderi N, Siggers P, et al. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet. 1998;7:737-42 pubmed
    ..Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11...
  2. Greenfield A, Scott D, Pennisi D, Ehrmann I, Ellis P, Cooper L, et al. An H-YDb epitope is encoded by a novel mouse Y chromosome gene. Nat Genet. 1996;14:474-8 pubmed
    ..We identify the peptide WMHHNMDLI derived from the UTY protein as an H-Y epitope, H-YDb. Our data formally demonstrate that H-Y antigen is the product of more than one gene on the Y chromosome. ..
  3. Mansour A, Gafni O, Weinberger L, Zviran A, Ayyash M, Rais Y, et al. The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature. 2012;488:409-13 pubmed publisher
    ..Here we show in mice and humans that the histone H3 methylated Lys?27 (H3K27) demethylase Utx (also known as Kdm6a) regulates the efficient induction, rather than maintenance, of pluripotency...
  4. Lee S, Lee J, Lee S. UTX, a histone H3-lysine 27 demethylase, acts as a critical switch to activate the cardiac developmental program. Dev Cell. 2012;22:25-37 pubmed publisher
    ..Here we show that UTX, a H3K27 demethylase, acts as a critical switch to promote a cardiac-specific gene program...
  5. Terashima M, Ishimura A, Yoshida M, Suzuki Y, Sugano S, Suzuki T. The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase. Biochem Biophys Res Commun. 2010;399:238-44 pubmed publisher
    b>Utx is a candidate tumor suppressor gene that encodes histone H3 lysine 27 (H3K27) demethylase...
  6. Seenundun S, Rampalli S, Liu Q, Aziz A, Palii C, Hong S, et al. UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J. 2010;29:1401-11 pubmed publisher
    ..Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis...
  7. Xu J, Burgoyne P, Arnold A. Sex differences in sex chromosome gene expression in mouse brain. Hum Mol Genet. 2002;11:1409-19 pubmed
    ..Six X-linked homologues (Usp9x, Ube1x, Smcx, Eif2s3x, Utx and Dbx) were also expressed in brain, and in adulthood all of these transcripts were expressed at significantly ..
  8. Chakroun I, Yang D, Girgis J, Gunasekharan A, Phenix H, Kærn M, et al. Genome-wide association between Six4, MyoD, and the histone demethylase Utx during myogenesis. FASEB J. 2015;29:4738-55 pubmed publisher
    ..adult myoblasts, the cooperation between Six4 and MyoD is associated with chromatin repressive mark removal by Utx, a demethylase of histone H3 trimethylated at lysine 27...
  9. Naruse C, Shibata S, Tamura M, Kawaguchi T, Abe K, Sugihara K, et al. New insights into the role of Jmjd3 and Utx in axial skeletal formation in mice. FASEB J. 2017;31:2252-2266 pubmed publisher
    Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3...
  10. Dahl J, Jung I, Aanes H, Greggains G, Manaf A, Lerdrup M, et al. Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature. 2016;537:548-552 pubmed publisher
    ..Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT. ..
  11. Sessa A, Ciabatti E, Drechsel D, Massimino L, Colasante G, Giannelli S, et al. The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways. Cereb Cortex. 2017;27:3378-3396 pubmed publisher
    ..These data identify TBR2 as a major determinant of the INP-specific traits by regulating both genetic and epigenetic pathways. ..
  12. 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
    ..On a macromolecular level, this mechamism involves Kdm6a down-regulation after long-term exposure to PM 2...
  13. Faralli H, Wang C, Nakka K, Benyoucef A, Sebastian S, Zhuang L, et al. UTX demethylase activity is required for satellite cell-mediated muscle regeneration. J Clin Invest. 2016;126:1555-65 pubmed publisher
    The X chromosome-encoded histone demethylase UTX (also known as KDM6A) mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish transcriptionally permissive chromatin...
  14. Cook K, Shpargel K, Starmer J, Whitfield Larry F, Conley B, Allard D, et al. T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX. Immunity. 2015;43:703-14 pubmed publisher
    ..We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T follicular helper (Tfh) cell responses that are essential ..
  15. Borensztein M, Okamoto I, Syx L, Guilbaud G, Picard C, Ancelin K, et al. Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass. Nat Commun. 2017;8:1297 pubmed publisher
    ..We further show that in UTX H3K27 histone demethylase mutant embryos, these genes are even more slowly reactivated, suggesting that these genes ..
  16. Messer H, Jacobs D, Dhummakupt A, Bloom D. Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons. J Virol. 2015;89:3417-20 pubmed publisher
    ..Here we demonstrate that GSK-J4, a specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits HSV-1 reactivation from sensory neurons in vitro...
  17. Van der Meulen J, Sanghvi V, Mavrakis K, Durinck K, Fang F, Matthijssens F, et al. The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia. Blood. 2015;125:13-21 pubmed publisher
    ..report somatic loss-of-function mutations in the X-linked histone H3K27me3 demethylase ubiquitously transcribed X (UTX) chromosome, in human T-ALL...
  18. Shpargel K, Starmer J, Yee D, Pohlers M, Magnuson T. KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development. PLoS Genet. 2014;10:e1004507 pubmed publisher
    ..have taken a mouse genetics approach to remove activity of both H3K27 demethylases of the Kdm6 gene family, Utx (Kdm6a, X-linked gene) and Jmjd3 (Kdm6b, autosomal gene)...
  19. Liu J, Mercher T, Scholl C, Brumme K, Gilliland D, Zhu N. A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells. Exp Hematol. 2012;40:487-98.e3 pubmed publisher
    Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), an H3K27Me2/3 demethylase, has been implicated in development, self-renewal, and differentiation of various organs and embryonic stem cells through chromatin ..
  20. Wolstenholme J, Rissman E, Bekiranov S. Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes. Genes Brain Behav. 2013;12:166-80 pubmed publisher
    ..Our results also indicate an interaction between gonadal development and sex chromosome number that could further elucidate the role of sex chromosome genes and hormones in the sexual differentiation of behavior. ..
  21. Shaw T, Martin P. Epigenetic reprogramming during wound healing: loss of polycomb-mediated silencing may enable upregulation of repair genes. EMBO Rep. 2009;10:881-6 pubmed publisher
    ..Suz12 are significantly downregulated during murine skin repair, whereas the newly described demethylases Jmjd3 and Utx are markedly upregulated...
  22. Li Q, Wang H, Chepelev I, Zhu Q, Wei G, Zhao K, et al. Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development. PLoS Genet. 2014;10:e1004524 pubmed publisher
    ..Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development. ..
  23. Mann K, Ward J, Yew C, Kovochich A, Dawson D, Black M, et al. Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma. Proc Natl Acad Sci U S A. 2012;109:5934-41 pubmed publisher
    ..Importantly, 10% of the CCGs are involved in chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1, ..
  24. 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
    Histone methylation is associated with various biological and pathological processes including cancer development. KDM6A is a candidate tumor suppressor gene that encodes a histone H3 lysine 27 (H3K27) demethylase...
  25. Yoo K, Oh S, Kang K, Wang C, Robinson G, Ge K, et al. Histone Demethylase KDM6A Controls the Mammary Luminal Lineage through Enzyme-Independent Mechanisms. Mol Cell Biol. 2016;36:2108-20 pubmed publisher
    ..We have now demonstrated an essential role for the H3K27me3 demethylase KDM6A in generating a balanced alveolar compartment...
  26. 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
    ..Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300...
  27. Manna S, Kim J, Baugé C, Cam M, Zhao Y, Shetty J, et al. Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation. Nat Commun. 2015;6:8152 pubmed publisher
    ..To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4(+) T-cell precursors...
  28. Zha L, Li F, Wu R, Artinian L, Rehder V, Yu L, et al. The Histone Demethylase UTX Promotes Brown Adipocyte Thermogenic Program Via Coordinated Regulation of H3K27 Demethylation and Acetylation. J Biol Chem. 2015;290:25151-63 pubmed publisher
    ..We have discovered that ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase for di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), plays a potential role in ..
  29. Berletch J, Deng X, Nguyen D, Disteche C. Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A. PLoS Genet. 2013;9:e1003489 pubmed publisher
    ..that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression...
  30. Yang D, Okamura H, Teramachi J, Haneji T. Histone demethylase Utx regulates differentiation and mineralization in osteoblasts. J Cell Biochem. 2015;116:2628-36 pubmed publisher
    ..by specific histone demethylases including ubiquitously transcribed tetratricopeptide repeat X chromosome (Utx). However, the role of Utx in osteoblast differentiation remains unknown...
  31. Lee J, Wang C, Xu S, Cho Y, Wang L, Feng X, et al. H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. elife. 2013;2:e01503 pubmed publisher
    ..Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01503.001. ..
  32. Iida A, Iwagawa T, Kuribayashi H, Satoh S, Mochizuki Y, Baba Y, et al. Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells. Proc Natl Acad Sci U S A. 2014;111:3751-6 pubmed publisher
    ..We propose that lineage-specific H3K27me3 demethylation of critical gene loci by spatiotemporal-specific Jmjd3 expression is required for appropriate maturation of retinal cells. ..
  33. Shpargel K, Starmer J, Wang C, Ge K, Magnuson T. UTX-guided neural crest function underlies craniofacial features of Kabuki syndrome. Proc Natl Acad Sci U S A. 2017;114:E9046-E9055 pubmed publisher
    ..a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D)...
  34. Kalantry S, Purushothaman S, Bowen R, Starmer J, Magnuson T. Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation. Nature. 2009;460:647-51 pubmed publisher
    ..Xp-linked gene silencing associated with mouse imprinted XCI, therefore, can initiate in the embryo independently of Xist RNA. ..
  35. Ota K, Tong K, Goto K, Tomida S, Komuro A, Wang Z, et al. The H3K27 demethylase, Utx, regulates adipogenesis in a differentiation stage-dependent manner. PLoS ONE. 2017;12:e0173713 pubmed publisher
    ..H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes...
  36. Li X, Zhang Q, Shi Q, Liu Y, Zhao K, Shen Q, et al. Demethylase Kdm6a epigenetically promotes IL-6 and IFN-β production in macrophages. J Autoimmun. 2017;80:85-94 pubmed publisher
    ..Demethylase Kdm6a promotes gene transcription in cell-lineage specification through demethylating histone H3 lysine di/tri-..
  37. Halstead A, Kapadia C, Bolzenius J, Chu C, Schriefer A, Wartman L, et al. Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation. elife. 2017;6: pubmed publisher
    ..Similarly, mutant RXRA stimulates growth-factor-independent growth of Trp53/Kdm6a null bladder organoids...
  38. Beyaz S, Kim J, Pinello L, Xifaras M, Hu Y, Huang J, et al. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017;18:184-195 pubmed publisher
    ..Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression ..
  39. Mugford J, Yee D, Magnuson T. Failure of extra-embryonic progenitor maintenance in the absence of dosage compensation. Development. 2012;139:2130-8 pubmed publisher
    ..Conversely, unlike the epiblast, in which XCI is not required for progenitor cell maintenance, we demonstrate that dosage compensation is indispensable for the maintenance of trophoblast progenitors. ..
  40. Yang L, Song L, Liu X, Xia Q, Bai L, Gao L, et al. The Maternal Effect Genes UTX and JMJD3 Play Contrasting Roles in Mus musculus Preimplantation Embryo Development. Sci Rep. 2016;6:26711 pubmed publisher
    ..We also determined that H3K27me3-specific demethylases, UTX and JMJD3, were observed at high transcript and protein levels in mouse preimplantation embryos...
  41. Dhar S, Lee S, Chen K, Zhu G, Oh W, Allton K, et al. An essential role for UTX in resolution and activation of bivalent promoters. Nucleic Acids Res. 2016;44:3659-74 pubmed publisher
    ..Here, we show that the H3K27 demethylase UTX (also called KDM6A) is required for the resolution and activation of numerous retinoic acid (RA)-inducible bivalent genes during the ..
  42. Hofstetter C, Kampka J, Huppertz S, Weber H, Schlosser A, Müller A, et al. Inhibition of KDM6 activity during murine ESC differentiation induces DNA damage. J Cell Sci. 2016;129:788-803 pubmed publisher
    ..Here, we have analysed the contribution of the H3K27me2- and H3K27me23-specific demethylases KDM6A and KDM6B to murine ESC differentiation by employing the GSK-J4 inhibitor, which is specific for KDM6 proteins, ..
  43. Scoville D, Cyphert H, Liao L, Xu J, Reynolds A, Guo S, et al. MLL3 and MLL4 Methyltransferases Bind to the MAFA and MAFB Transcription Factors to Regulate Islet β-Cell Function. Diabetes. 2015;64:3772-83 pubmed publisher
    ..We propose that MLL3 and MLL4 are broadly required for controlling MAFA and MAFB transactivation during development and postnatally. ..
  44. Ntziachristos P, Tsirigos A, Welstead G, Trimarchi T, Bakogianni S, Xu L, et al. Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature. 2014;514:513-7 pubmed publisher
    ..Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL...
  45. Thieme S, Gyárfás T, Richter C, Ozhan G, Fu J, Alexopoulou D, et al. The histone demethylase UTX regulates stem cell migration and hematopoiesis. Blood. 2013;121:2462-73 pubmed publisher
    ..cell-derived factor-1 (SDF-1) migration screening assay, we identified the histone 3 lysine 27 demethylase UTX (Kdm6a) as a novel regulator for hematopoietic cell migration...