TWIST1 methylation by SETD6 selectively antagonizes LINC-PINT expression in glioma

Lee Admoni-Elisha, Tzofit Elbaz, Anand Chopra, Guy Shapira, Mark T. Bedford, Christopher J. Fry, Noam Shomron, Kyle Biggar, Michal Feldman, Dan Levy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in glioma patients. RNA-seq analysis in U251 glioma cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby promoting EMT in glioma. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.

Original languageEnglish
Pages (from-to)6903-6918
Number of pages16
JournalNucleic Acids Research
Issue number12
StatePublished - 8 Jul 2022


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