An Amino Terminal Phosphorylation Motif Regulates Intranuclear Compartmentalization of Olig2 in Neural Progenitor Cells

Abstract

The bHLH transcription factor Olig2 is expressed in cycling neural progenitor cells but also in terminally differentiated

Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-β Pathway

“…To scrutinize the downstream mechanisms through which OLIG2 governs invasion, we focused our attention on TGFβ2 for two reasons: Tgfβ2 is a direct genetic target of Olig2 in normal neural progenitor cells (Meijer et al, 2014) and the TGFβ pathway plays an important role in invasion of tumor cells in several solid cancers, including GBM (Anido et al, 2010, Rich, 2003, Weller et al, 2001, Wick et al, 2001). Analysis of ChIP-seq tracks from Meijer et al demonstrated that both phosphorylated and unphosphorylated forms of Olig2 associate with the Tgfβ2 locus (Figures 5E and 5F) and regulate its expression in normal neural progenitor cells (Meijer et al, 2014).…”

“…Analysis of ChIP-seq tracks from Meijer et al demonstrated that both phosphorylated and unphosphorylated forms of Olig2 associate with the Tgfβ2 locus (Figures 5E and 5F) and regulate its expression in normal neural progenitor cells (Meijer et al, 2014). ChIP assay with Olig2 and H3K27ac antibodies confirmed association of both TPM and TPN mutants with Tgfβ2 enhancer region in mGSCs (Figure 5F) and we found significant enrichment of the active enhancer histone mark (H3K27ac) at the Tgfβ2 locus (ChIP-seq track for H3K27ac from (Mateo et al, 2015)) in TPN cells compared to that in TPM cells (Figures 5E and 5F).…”

“…Quantitative PCR was performed using inventoried Taqman assays for respective target genes and housekeeping control genes (HPRT or 18S) on the QuantStudio 6 Flex Real-Time PCR System (Life Technologies; ThermoFisher Scientific Inc.). ChIP experiments were performed as described previously (Meijer et al, 2014). Primers details provided in supplementary materials.…”

A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment

“…Loss of Trp53 resulted in a 6-fold increased Wnt7b transcript level, suggesting that Olig2-driven upregulation of Wnt7b is inhibited by p53 (Figure 3D). In order to confirm this antagonism, we showed that using DNA-binding mutant of Olig2 (Olig2 DBM ) (Mehta et al, 2011; Meijer et al, 2014) p53 binding on Wnt7b was increased (Figure 3E). In addition, we demonstrated that the binding site of Olig2 within Wnt7b is functional as DBM failed to regulate Wnt7b expression, as well as Sox2 and Pdgfra (Figure 3F).…”

Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma

“…The Olig2-targeted genes were highly enriched in the enhancer regions, marked by the activating histone mark H3K27ac, in the genome of tumor tissues (Figure 6D). When comparing the Olig2 occupancy profiles with those of Olig2-enriched neural progenitor cells (NPCs) (Meijer et al, 2014), we detected a unique subset of gene promoters/enhancers exhibiting strong Olig2 enrichment in the neoplasm but not in normal NPCs (Figure 6E). A cohort of Olig2-targeted sites was identified specifically in tumors (Figure 6F), but not in Olig2-enriched NPCs or OPCs (Yu et al, 2013).…”