| First Author | Yamanaka T | Year | 2016 |
| Journal | FEBS J | Volume | 283 |
| Issue | 6 | Pages | 1077-87 |
| PubMed ID | 26756308 | Mgi Jnum | J:249187 |
| Mgi Id | MGI:6093363 | Doi | 10.1111/febs.13650 |
| Citation | Yamanaka T, et al. (2016) Genome-wide analyses in neuronal cells reveal that upstream transcription factors regulate lysosomal gene expression. FEBS J 283(6):1077-87 |
| abstractText | UNLABELLED: The upstream transcription factors (USFs) USF1 and USF2 are ubiquitously expressed transcription factors that are 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 responses 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. 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 array analysis using a neuronal cell line subsequently revealed that knockdown of USFs de-regulated lysosomal gene expression. Altered expression was validated by quantitative RT-PCR, supporting the conclusion that USFs regulate lysosomal gene expression. Furthermore, USF knockdown slightly increased LysoTracker Red 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. DATABASE: The data for the gene expression array and ChIP-chip have been submitted to the Gene Expression Omnibus (GEO) under accession numbers GSE76615 and GSE76616, respectively. |
