The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity

Publication date: 11 January 2016
Source:Cancer Cell, Volume 29, Issue 1
Author(s): BaoHan T. Vo, Elmar Wolf, Daisuke Kawauchi, Anneli Gebhardt, Jerold E. Rehg, David Finkelstein, Susanne Walz, Brian L. Murphy, Yong Ha Youn, Young-Goo Han, Martin Eilers, Martine F. Roussel
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.

Graphical abstract

Teaser

Myc and MycN have many similar functions but they are differentially expressed among subtypes of human medulloblastoma (MB) and they induce different experimental mouse MB subtypes. Vo et al. show that these differences are partly due to their differential binding of Miz1 and repressing gene expression.


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