EPCO-05. GENOME-WIDE ANALYSIS OF TEAD1 OCCUPANCY IN BIOLOGICALLY DISTINCT GLIOBLASTOMA SAMPLES. (12th November 2021)

• Record Type: Journal Article
• Authors: Joshi, Tanvi; Nudelman, German; Zaslavsky, Elena; Tsankova, Nadejda
• Is Part Of: Neuro-oncology. Volume 23: Supplement 6(2021)
• Page Start: vi2
• Page End: vi2
• Publication Date: 2021-11-12
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab196.004
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: The diffusely infiltrative nature of glioblastoma (GBM) cells is a major contributor to the disease's aggressive behavior, including its rapid progression and therapeutic resistance. Moreover, current treatment options do not target the invasive nature of GBM. Recent chromatin accessibility studies prioritized enrichment of the TEAD1 transcription factor motif in glioblastoma stem cell biology and subsequent knockout and overexpression studies confirmed a critical role for TEAD1 in GBM migration, in vitro and in vivo. However, the downstream mechanisms through which TEAD1 regulates GBM cell migration remain poorly understood. In this study, we performed chromatin immunoprecipitation (ChIP-seq) using TEAD1-specific antibody and IgG as non-specific binding control, to characterize TEAD1 occupancy across GBM samples with unique genomic alterations. ChIP-seq peaks were called using MACS2, filtered for duplicates and blacklisted regions, and normalized per sample to their respective genomic input. Initial functional enrichment analyses were performed on three GBM samples with the highest number of TEAD1 occupancy peaks using CistromeGO, which ranked genes based on their TEAD1-specific regulatory potential (RP) score, as a function of peak number and distance from the transcription start site. Analyses of the top 1000 genes with highest TEAD1 RP scores identified 132 common targets across all samples, including known TEAD target genes ETV1 and Cyr61, which related to angiogenesis, cadherin and integrin signaling, cell adhesion, and chromatin regulation gene ontology terms, among others. Interestingly, KEGG pathway analysis also revealed Hippo pathway enrichment across all GBM samples, suggesting a possible TEAD1 regulatory feedback loop in GBM. Analysis of TEAD1 ChIP-seq peaks in non-GBM negative control tissue did not show functional enrichment for any of the terms seen in the GBM samples. Ongoing analyses are focused on characterizing TEAD1 occupancy at active cis-regulatory regions using parallel H3K27ac ChIP-seq data, in order to prioritize the most salient TEAD1-regulatory targets in GBM.