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Review

Histone-Modifying Enzymes: Regulators of Developmental Decisions and Drivers of Human Disease

, , &
Pages 163-177 | Published online: 27 Mar 2012

References

  • Lessard JA , CrabtreeGR. Chromatin regulatory mechanisms in pluripotency. Annu. Rev. Cell Dev. Biol.26 , 503–532 (2010).
  • Mills AA . Throwing the cancer switch. reciprocal roles of polycomb and trithorax proteins. Nat. Rev. Cancer10(10) , 669–682 (2010).
  • Ringrose L , ParoR. Epigenetic regulation of cellular memory by the polycomb and trithorax group proteins. Annu. Rev. Genet.38 , 413–443 (2004).
  • Soshnikova N , DubouleD. Epigenetic regulation of vertebrate Hox genes: a dynamic equilibrium. Epigenetics4(8) , 537–540 (2009).
  • Mallo M , WellikDM, DeschampsJ. Hox genes and regional patterning of the vertebrate body plan. Dev. Biol.344(1) , 7–15 (2010).
  • Shah N , SukumarS. The Hox genes and their roles in oncogenesis. Nat. Rev. Cancer10(5) , 361–371 (2010).
  • Torres-Padilla ME , ParfittDE, KouzaridesT, Zernicka-GoetzM. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature445(7124) , 214–218 (2007).
  • Wu Q , BruceAW, JedrusikA et al. CARM1 is required in embryonic stem cells to maintain pluripotency and resist differentiation. Stem Cells 27(11) , 2637–2645 (2009).
  • Parfitt DE , Zernicka-GoetzM. Epigenetic modification affecting expression of cell polarity and cell fate genes to regulate lineage specification in the early mouse embryo. Mol. Biol. Cell21(15) , 2649–2660 (2010).
  • O‘neill LP , VermilyeaMD, TurnerBM. Epigenetic characterization of the early embryo with a chromatin immunoprecipitation protocol applicable to small cell populations. Nat. Genet.38(7) , 835–841 (2006).
  • Ang YS , TsaiSY, LeeDF et al. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145(2) , 183–197 (2011).
  • Dou Y , MilneTA, RuthenburgAJ et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat. Struct. Mol. Biol. 13(8) , 713–719 (2006).
  • Boyer LA , PlathK, ZeitlingerJ et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441(7091) , 349–353 (2006).
  • Conerly MI , MacquarrieKL, FongAP, YaoZ, TapscottSJ. Polycomb-mediated repression during terminal differentiation: what don‘t you want to be when you grow up? Genes Dev.25(10) , 997–1003 (2011).
  • Lee TI , JennerRG, BoyerLA et al. Control of developmental regulators by polycomb in human embryonic stem cells. Cell 125(2) , 301–313 (2006).
  • Lee MG , VillaR, TrojerP et al. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318(5849) , 447–450 (2007).
  • Agger K , CloosPA, ChristensenJ et al. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449(7163) , 731–734 (2007).
  • Lan F , BaylissPE, RinnJL et al. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449(7163) , 689–694 (2007).
  • Peng JC , ValouevA, SwigutT et al. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 139(7) , 1290–1302 (2009).
  • Pasini D , CloosPA, WalfridssonJ et al. JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells. Nature 464(7286) , 306–310 (2010).
  • Shen X , KimW, FujiwaraY et al. Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell 139(7) , 1303–1314 (2009).
  • Endoh M , EndoTA, EndohT et al. Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity. Development 135(8) , 1513–1524 (2008).
  • Stock JK , GiadrossiS, CasanovaM et al. Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat. Cell Biol. 9(12) , 1428–1435 (2007).
  • Alder O , LavialF, HelnessA et al. Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development 137(15) , 2483–2492 (2010).
  • Loh YH , ZhangW, ChenX, GeorgeJ, NgHH. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev.21(20) , 2545–2557 (2007).
  • Feldman N , GersonA, FangJ et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell Biol. 8(2) , 188–194 (2006).
  • Epsztejn-Litman S , FeldmanN, Abu-RemailehM et al. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat. Struct. Mol. Biol.15(11) , 1176–1183 (2008).
  • Szutorisz H , CanzonettaC, GeorgiouA, ChowCM, ToraL, DillonN. Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol. Cell Biol.25(5) , 1804–1820 (2005).
  • Pasini D , MalatestaM, JungHR et al. Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res. 38(15) , 4958–4969 (2010).
  • Yao TP , OhSP, FuchsM et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93(3) , 361–372 (1998).
  • Xu CR , ColePA, MeyersDJ, KormishJ, DentS, ZaretKS. Chromatin ‘prepattern‘ and histone modifiers in a fate choice for liver and pancreas. Science332(6032) , 963–966 (2011).
  • Ma P , SchultzRM. Histone deacetylase 1 (HDAC1) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev. Biol.319(1) , 110–120 (2008).
  • Brunmeir R , LaggerS, SeiserC. Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. Int. J. Dev. Biol.53(2–3) , 275–289 (2009).
  • Kaji K , NicholsJ, HendrichB. Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development134(6) , 1123–1132 (2007).
  • Marino S , NusseR. Mutants in the mouse NuRD/Mi2 component P66α are embryonic lethal. PLoS ONE2(6) , e519 (2007).
  • Zhu D , FangJ, LiY, ZhangJ. Mbd3, a component of NuRD/Mi-2 complex, helps maintain pluripotency of mouse embryonic stem cells by repressing trophectoderm differentiation. PLoS ONE4(11) , e7684 (2009).
  • Liang J , WanM, ZhangY et al. Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nat. Cell Biol. 10(6) , 731–739 (2008).
  • Dovey OM , FosterCT, CowleySM. Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc. Natl Acad. Sci. USA107(18) , 8242–8247 (2010).
  • Lyu J , JhoEH, LuW. Smek promotes histone deacetylation to suppress transcription of Wnt target gene brachyury in pluripotent embryonic stem cells. Cell Res.21(6) , 911–921 (2011).
  • Addis RC , PrasadMK, YochemRL et al. OCT3/4 regulates transcription of histone deacetylase 4 (Hdac4) in mouse embryonic stem cells. J. Cell Biochem. 111(2) , 391–401 (2010).
  • Montgomery RL , DavisCA, PotthoffMJ et al. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev. 21(14) , 1790–1802 (2007).
  • Trivedi CM , LuoY, YinZ et al. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3β activity. Nat. Med. 13(3) , 324–331 (2007).
  • Broide RS , RedwineJM, AftahiN, YoungW, BloomFE, WinrowCJ. Distribution of histone deacetylases 1–11 in the rat brain. J. Mol. Neurosci.31(1) , 47–58 (2007).
  • Akhtar MW , RaingoJ, NelsonED et al. Histone deacetylases 1 and 2 form a developmental switch that controls excitatory synapse maturation and function. J. Neurosci. 29(25) , 8288–8297 (2009).
  • Quinti L , ChopraV, RotiliD et al. Evaluation of histone deacetylases as drug targets in Huntington‘s disease models. Study of HDACs in brain tissues from R6/2 and CAG140 knock-in HD mouse models and human patients and in a neuronal HD cell model. PLoS Curr. 2 , pii: RRN1172 (2010).
  • Helmlinger D , HardyS, EberlinA, DevysD, ToraL. Both normal and polyglutamine-expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase – containing complexes. Biochem. Soc. Symp.73 , 155–163 (2006).
  • Mcmahon SJ , Pray-GrantMG, SchieltzD, YatesJR 3rd, Grant PA. Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity. Proc. Natl Acad. Sci. USA102(24) , 8478–8482 (2005).
  • Palhan VB , ChenS, PengGH et al. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc. Natl Acad. Sci. USA 102(24) , 8472–8477 (2005).
  • David G , AbbasN, StevaninG et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat. Genet. 17(1) , 65–70 (1997).
  • David G , DurrA, StevaninG et al. Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Hum. Mol. Genet. 7(2) , 165–170 (1998).
  • Chen YC , GatchelJR, LewisRW et al. Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum. Mol. Genet. 21(2) , 394–405 (2012).
  • Caretti G , Di Padova M, Micales B, Lyons Ge, Sartorelli V. The polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev.18(21) , 2627–2638 (2004).
  • Rampalli S , LiL, MakE et al. p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation. Nat. Struct. Mol. Biol. 14(12) , 1150–1156 (2007).
  • Acharyya S , SharmaSM, ChengAS et al. TNF inhibits Notch-1 in skeletal muscle cells by Ezh2 and DNA methylation mediated repression: implications in duchenne muscular dystrophy. PLoS ONE 5(8) , e12479 (2010).
  • Chen H , GuX, SuIH et al. Polycomb protein Ezh2 regulates pancreatic β-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev. 23(8) , 975–985 (2009).
  • Dhawan S , TschenSI, BhushanA. Bmi-1 regulates the Ink4a/Arf locus to control pancreatic β-cell proliferation. Genes Dev.23(8) , 906–911 (2009).
  • Ezhkova E , PasolliHA, ParkerJS et al. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 136(6) , 1122–1135 (2009).
  • Leung C , LingbeekM, ShakhovaO et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428(6980) , 337–341 (2004).
  • Roman-Trufero M , Mendez-GomezHR, PerezC et al. Maintenance of undifferentiated state and self-renewal of embryonic neural stem cells by Polycomb protein Ring1B. Stem Cells 27(7) , 1559–1570 (2009).
  • Sher F , RosslerR, BrouwerN, BalasubramaniyanV, BoddekeE, CoprayS. Differentiation of neural stem cells into oligodendrocytes: involvement of the polycomb group protein Ezh2. Stem Cells26(11) , 2875–2883 (2008).
  • Pasini D , BrackenAP, HansenJB, CapilloM, HelinK. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol. Cell Biol.27(10) , 3769–3779 (2007).
  • Hirabayashi Y , SuzkiN, TsuboiM et al. Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron 63(5) , 600–613 (2009).
  • Luna-Fineman S , ShannonKM, LangeBJ. Childhood monosomy 7: epidemiology, biology, and mechanistic implications. Blood85(8) , 1985–1999 (1995).
  • Dohner K , BrownJ, HehmannU et al. Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders. Blood 92(11) , 4031–4035 (1998).
  • Iwase S , LanF, BaylissP et al. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 128(6) , 1077–1088 (2007).
  • Kleine-Kohlbrecher D , ChristensenJ, VandammeJ et al. A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation. Mol. Cell 38(2) , 165–178 (2010).
  • Van Bokhoven H , KramerJM. Disruption of the epigenetic code. an emerging mechanism in mental retardation. Neurobiol. Dis.39(1) , 3–12 (2010).
  • Shima Y , KitabayashiI. Deregulated transcription factors in leukemia. Int. J. Hematol.94(2) , 134–141 (2011).
  • Kobelka CE . Exome sequencing: expanding the genetic testing toolbox. Clin. Genet.78(2) , 132–134 (2010).
  • Cooper GM , ShendureJ. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat. Rev. Genet.12(9) , 628–640 (2011).
  • Bamshad MJ , NgSB, BighamAW et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat. Rev. Genet. 12(11) , 745–755 (2011).
  • Vogelstein B , KinzlerKW. Cancer genes and the pathways they control. Nat. Med.10(8) , 789–799 (2004).
  • Liu H , ChengEH, HsiehJJ. MLL fusions: pathways to leukemia. Cancer Biol. Ther.8(13) , 1204–1211 (2009).
  • Marschalek R . Mechanisms of leukemogenesis by MLL fusion proteins. Br. J. Haematol.152(2) , 141–154 (2010).
  • Guenther MG , LawtonLN, RozovskaiaT et al. Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia. Genes Dev. 22(24) , 3403–3408 (2008).
  • Morin RD , Mendez-LagoM, MungallAJ et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 476(7360) , 298–303 (2011).
  • Pasqualucci L , TrifonovV, FabbriG et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat. Genet. 43(9) , 830–837 (2011).
  • Hess JL , YuBD, LiB, HansonR, KorsmeyerSJ. Defects in yolk sac hematopoiesis in Mll-null embryos. Blood90(5) , 1799–1806 (1997).
  • Heuser M , YapDB, LeungM et al. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 113(7) , 1432–1443 (2009).
  • Velichutina I , ShaknovichR, GengH et al. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood 116(24) , 5247–5255 (2010).
  • Chase A , CrossNC. Aberrations of EZH2 in cancer. Clin. Cancer Res.17(9) , 2613–2618 (2011).
  • Morin RD , JohnsonNA, SeversonTM et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet. 42(2) , 181–185 (2010).
  • Yap DD , ChuJ, BergT et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 117(8) , 2451–2459 (2011).
  • Makishima H , JankowskaAM, TiuRV et al. Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies. Leukemia 24(10) , 1799–1804 (2010).
  • Nikoloski G , LangemeijerSM, KuiperRP et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat. Genet. 42(8) , 665–667 (2010).
  • Ernst T , ChaseAJ, ScoreJ et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat. Genet. 42(8) , 722–726 (2010).
  • Jankowska AM , MakishimaH, TiuRV et al. Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2 and DNMT3A. Blood 118(14) , 3932–3941 (2011).
  • Grossmann V , KohlmannA, EderC et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia 25(5) , 877–879 (2011).
  • Van Haaften G , DalglieshGL, DaviesH et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat. Genet. 41(5) , 521–523 (2009).
  • Chapman MA , LawrenceMS, KeatsJJ et al. Initial genome sequencing and analysis of multiple myeloma. Nature 471(7339) , 467–472 (2011).
  • Stec I , WrightTJ, Van Ommen GJ et al. WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf–Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma. Hum. Mol. Genet.7(7) , 1071–1082 (1998).
  • Martinez-Garcia E , PopovicR, MinDJ et al. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood 117(1) , 211–220 (2011).
  • Mullighan CG , ZhangJ, KasperLH et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature471(7337) , 235–239 (2011).
  • Pasqualucci L , Dominguez-SolaD, ChiarenzaA et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 471(7337) , 189–195 (2011).
  • Oike Y , TakakuraN, HataA et al. Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood 93(9) , 2771–2779 (1999).
  • Parsons DW , LiM, ZhangX et al. The genetic landscape of the childhood cancer medulloblastoma. Science 331(6016) , 435–439 (2011).
  • Northcott PA , NakaharaY, WuX et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat. Genet. 41(4) , 465–472 (2009).
  • Gui Y , GuoG, HuangY et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat. Genet. 43(9) , 875–878 (2011).
  • Dalgliesh GL , FurgeK, GreenmanC et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463(7279) , 360–363 (2010).
  • Varela I , TarpeyP, RaineK et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469(7331) , 539–542 (2011).
  • Petrij F , GilesRH, DauwerseHG et al. Rubinstein–Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376(6538) , 348–351 (1995).
  • Roelfsema JH , PetersDJ. Rubinstein–Taybi syndrome: clinical and molecular overview. Expert Rev. Mol. Med.9(23) , 1–16 (2007).
  • De Sario A . Clinical and molecular overview of inherited disorders resulting from epigenomic dysregulation. Eur. J. Med. Genet.52(6) , 363–372 (2009).
  • Alarcon JM , MalleretG, TouzaniK et al. Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein–Taybi syndrome and its amelioration. Neuron 42(6) , 947–959 (2004).
  • Bartholdi D , RoelfsemaJH, PapadiaF et al. Genetic heterogeneity in Rubinstein–Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J. Med. Genet. 44(5) , 327–333 (2007).
  • Miller RW , RubinsteinJH. Tumors in Rubinstein–Taybi syndrome. Am. J. Med. Genet.56(1) , 112–115 (1995).
  • Kleefstra T , SmidtM, BanningMJ et al. Disruption of the gene Euchromatin histone methyl transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome. J. Med. Genet. 42(4) , 299–306 (2005).
  • Verhoeven WM , EggerJI, VermeulenK, Van De Warrenburg BP, Kleefstra T. Kleefstra syndrome in three adult patients: further delineation of the behavioral and neurological phenotype shows aspects of a neurodegenerative course. Am. J. Med. Genet. A155(10) , 2409–2415 (2011).
  • Cheung HC , YatsenkoSA, KadapakkamM et al. Constitutional tandem duplication of 9q34 that truncates EHMT1 in a child with ganglioglioma. Pediatr. Blood Cancer 58(5) , 801–805 (2012).
  • Jensen LR , AmendeM, GurokU et al. Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation. Am. J. Hum. Genet. 76(2) , 227–236 (2005).
  • Rujirabanjerd S , NelsonJ, TarpeyPS et al. Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation. Eur. J. Hum. Genet. 18(3) , 330–335 (2010).
  • Tahiliani M , MeiP, FangR et al. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 447(7144) , 601–605 (2007).
  • Ng SB , BighamAW, BuckinghamKJ et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42(9) , 790–793 (2010).
  • Paulussen AD , StegmannAP, BlokMJ et al. MLL2 mutation spectrum in 45 patients with Kabuki syndrome. Hum. Mutat.32(2) , E2018–E2025 (2010).
  • Hannibal MC , BuckinghamKJ, NgSB et al. Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am. J. Med. Genet. A 155A(7) , 1511–1516 (2011).
  • Li Y , BogershausenN, AlanayY et al. A mutation screen in patients with Kabuki syndrome. Hum. Genet. 130(6) , 715–724 (2011).
  • Niikawa N , MatsuuraN, FukushimaY, OhsawaT, KajiiT. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J. Pediatr.99(4) , 565–569 (1981).
  • Kuroki Y , SuzukiY, ChyoH, HataA, MatsuiI. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J. Pediatr.99(4) , 570–573 (1981).
  • Pless B , OehmC, KnauerS, StauberRH, DingermannT, MarschalekR. The heterodimerization domains of MLL-FYRN and FYRC – are potential target structures in t(4;11) leukemia. Leukemia25(4) , 663–670 (2011).

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