title: The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity.
abstract: Four distinct subgroups of cerebellar medulloblastomas (MBs) differ in their histopathology, molecular profiles, and prognosis. c-Myc (Myc) or MycN overexpression in granule neuron progenitors (GNPs) induces Group 3 (G3) or Sonic Hedgehog (SHH) MBs, respectively. Differences in Myc and MycN transcriptional profiles depend, in part, on their interaction with Miz1, which binds strongly to Myc but not MycN, to target sites on chromatin. Myc suppresses ciliogenesis and reprograms the transcriptome of SHH-dependent GNPs through Miz1-dependent gene repression to maintain stemness. Genetic disruption of the Myc/Miz1 interaction inhibited G3 MB development. Target genes of Myc/Miz1 are repressed in human G3 MBs but not in other subgroups. Therefore, the Myc/Miz1 interaction is a defining hallmark of G3 MB development.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: BaoHan T
authors.initials: BT
authors.lastname: Vo
authors.affiliation: Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.|German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology (B062) Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawauchi
authors.affiliation: Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Anneli
authors.initials: A
authors.lastname: Gebhardt
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Jerold E
authors.initials: JE
authors.lastname: Rehg
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: David
authors.initials: D
authors.lastname: Finkelstein
authors.affiliation: Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str.6, 97080 Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walz
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Murphy
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Youn
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Young-Goo
authors.initials: YG
authors.lastname: Han
authors.affiliation: Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str.6, 97080 Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Martine F
authors.initials: MF
authors.lastname: Roussel
mesh_terms: D000818:Animals; D002528:Cerebellar Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics; D008527:Medulloblastoma / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D016271:Proto-Oncogene Proteins c-myc; C485521:Miz1 protein, mouse; D044767:Ubiquitin-Protein Ligases