ID4 function antagonizes OLIG1 and OLIG2 to suppressive aggressive glioma

ABSTRACT: The basic helix-loop-helix proteins Olig1 and Olig2 are expressed in high grade, aggressive human glioblastoma multiformes (GBMs). Here we investigated genetic mechanisms regulating Olig1/2 function during gliomagenesis. Although Olig2 function is necessary for early-aggressive tumor formation in a genetically relevant model of classic GBMs with intact p53 function, late-onset gliomas do eventually form. Using an unbiased approach, we identified Id4, encoding a negative HLH protein, as a gene target potently repressed by Olig2 in glioma progenitors. Although Id4 is thought to antagonize proneural genes involved in differentiation, we report a paradoxical role for Id4 in glioma. Genetic deletion of Id4 converts Olig2-/- gliomas to the early-aggressive form, and conversely, overexpression of Id4 inhibits intact Olig2 and prevents even late-onset tumors. Olig1 overexpression is sufficient for gliomagenesis in an Id4-dependent manner.  Together, these findings indicate that gliomagenic factors Olig1 and Olig2 are opposed by Id4 function, which acts as tumor suppressor in p53-intact gliomas.

ORGANISM(S): Mus musculus

PROVIDER: GSE44151 | GEO | 2018/01/02

SECONDARY ACCESSION(S): PRJNA188786

REPOSITORIES: GEO