Genome-wide analyses in neuronal cells reveal that USF transcription factors regulate lysosomal gene expression [Expression analysis]

ABSTRACT: The upstream stimulating factors (USFs) USF1 and USF2 are ubiquitously expressed transcription factors characterized by a conserved basic helix-loop-helix leucine zipper DNA-binding domain. They form homo- or heterodimers and recognize E-box motifs to modulate gene expression. They are known to regulate diverse cellular functions including the cell cycle, immune response and glucose-lipid metabolism, but their roles in neuronal cells remain to be clarified. Here, we performed chromatin immunoprecipitation of USF1 from mouse brain cortex preparations. Subsequent promoter array analysis (ChIP-chip) indicated that USF1 exclusively bound to the CACGTG E-box motifs in the proximal promoter regions. Importantly, functional annotation of the USF1-binding targets revealed an enrichment of genes related to lysosomal functions. Gene expression arrays using a neuronal cell line subsequently revealed that knockdown of USFs deregulated lysosomal gene expression. Altered expression was validated by quantitative RT-PCR, supporting the conclusion that USFs regulate lysosomal gene expression. Furthermore, USFs knockdown slightly increased LysoTracker staining, implying a role for USFs in modulating lysosomal homeostasis. Together, our comprehensive, genome-scale analyses identified lysosomal genes as targets of USFs in neuronal cells, suggesting a potential additional pathway of lysosomal regulation. Gene expression profiling of neuro2a cells knocking down USFs.

ORGANISM(S): Mus musculus

PROVIDER: GSE76615 | GEO | 2016/01/08

SECONDARY ACCESSION(S): PRJNA308177

REPOSITORIES: GEO