Menin is a Targetable Epigenetic Regulator in Glioblastoma (ChIP-Seq)

Glioblastomas (GBM) are highly lethal tumors that are refractory to treatment. Here we describe a novel approach to target the epigenetic landscape of GBM and destabilize the glioma progenitor program, leading to inhibition of tumor growth. This is achieved through disruption of the activities of menin, an orphan protein that we demonstrate to play a pro-oncogenic role in GBM. Using pharmacologic and genetic tools, we identify HMGN1, a nucleosome binding chromatin architectural protein as a novel partner for menin. Disruption of this interaction via a newly designed small molecule mimics the major effects of knocking out MEN1, particularly leading to the suppression of H3K27 acetylation marks at genes critical for glioma progenitor identity, as well as promising therapeutic in vivo activity. This work demonstrates a novel role for menin as an epigenetic co-regulator of maintenance and proliferation of glioma. Overall design: Chromatin Immunoprecipitation DNA sequencing (ChIP-seq) for Histone H3 Lysine 27 acetylation (H3K27ac) is performed with MEN1-WT, MEN1-KO and MY-182 treated glioblastoma cell.