UC San Diego

Glioblastoma multiforme, a form of malignant glioma, is a central nervous system (CNS) tumor associated with the worst prognosis in both adults and children. Effective treatments for this deadly cancer have continued to be elusive to this day. Several strategies have been employed to better understand malignant gliomas including genomics, cell survival, and cell fate determination. Previously we found that a glial cell determining factor, Nuclear Factor I-A (NFIA), is expressed in gliomas and has functional roles during glioma tumorigenesis. During CNS development, NFIA expression is regulated by distinct chromatin conformations that involve the transcription factors SOX9 and BRN2. The glial cell specific chromatin architecture is also present in glioma and modulation of the architecture has profound effects on tumor growth. Interestingly, the formation of this glial loop is not mediated by SOX9 and BRN2. A candidate factor for mediating formation of this chromatin architecture is the Mediator complex subunit 12 (MED12). Here we test whether MED12 is a component of the SOX9/BRN2complex, affects NFIA expression, and begin to determine what role MED12 plays in glioma tumorigenesis. Using dual gRNAs in a CRISPR/Cas9 system to delete MED12 expression from human glioma cell lines U87 and LN229, we found that MED12 is important for tumor growth, migration, and proliferation.