Identification of Genomic Targets of Transcription Factor Aebp1 and its role in Survival of Glioma Cells

Abstract

A recent transcriptome analysis of graded patient glioma samples led to identification of AEBP1 as one of the genes upregulated in majority of the primary GBM as against secondary GBM. Aebp1 is a transcriptional repressor that is involved in adipogenesis. It binds to AE-1 element present in the proximal promoter of aP2 gene that codes for fatty acid binding protein (FABP4). A comprehensive study was undertaken to elucidate the role of AEBP1 overexpression in glioblastoma. We employed complementary gene silencing approach to identify the genes that are perturbed in a glioma cell line (U87MG). A total of 734 genes were differentially regulated under these conditions (≥ 1.5-fold, P ≤ 0.05) belonging to different GO categories such as transcription regulation, cell growth, proliferation, differentiation, and apoptosis of which perturbation of 114 genes of these pathways were validated by quantitative real time PCR (qRT-PCR). This approach was subsequently combined with ChIP-chip technique using an Agilent human promoter tiling array to identify genomic binding loci of Aebp1 protein. A subset of these genes identified for Aebp1 occupancy was also validated by ChIP-PCR. Bioinformatics analysis of the promoters identified by ChIP-chip technique revealed a consensus motif GAAAT present in 66% of the identified genes. This consensus motif was experimentally validated by functional promoter assay using luciferase as the reporter gene. Both cellular proliferation and survival were affected in AEBP1-silenced U87MG and U138MG cell lines and a significant percentage of these cells were directed towards apoptosis.

A novel integrated gene coexpression analysis approach reveals a prognostic three-transcription-factor signature for glioma molecular subtypes

“…Similarly, SULT4A1, with lower expression in children brain tumor [39], is regulated positively by NFIL3 in normal samples while negatively by NFIL3 in NG group. The negative regulation relationship between NFIL3 and NGEF in NG group, and the lower expression of NGEF was also observed, which is consistent with the previous report [40]. …”

Computational Identification of Key Regulators in Two Different Colorectal Cancer Cell Lines

“…For the CMT-93-specific TFs, the analysis reported the master regulators Aebp1 (ACLP), Il2rg (gamma-c) and Mapk1 (ERK2), which reach 43, 36, and 31 TFs from the set, respectively. The first proposed master regulator, Aebp1, is known to act as a transcriptional repressor in adipogenesis (Ladha et al, 2012 ). Aebp1 is upregulated in the majority of the primary glioblastoma multiforme (GBM) and loss of Aebp1 function was shown to result in apoptosis (Ladha et al, 2012 ).…”

Association of adipocyte enhancer‐binding protein 1 with Alzheimer's disease pathology in human hippocampi

“…Regarding the constitutive expression of AEBP1 in brain tissue, previous reports have shown that AEBP1 protein is expressed in the choroid plexus of embryos and in some glioma cell lines . However, the expression profile of the AEBP1 protein in adult brains has not yet been examined.…”