2016年3月
Genome-wide analyses in neuronal cells reveal that upstream transcription factors regulate lysosomal gene expression
FEBS JOURNAL
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- 巻
- 283
- 号
- 6
- 開始ページ
- 1077
- 終了ページ
- 1087
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/febs.13650
- 出版者・発行元
- WILEY-BLACKWELL
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.
- リンク情報
- ID情報
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- DOI : 10.1111/febs.13650
- ISSN : 1742-464X
- eISSN : 1742-4658
- PubMed ID : 26756308
- Web of Science ID : WOS:000373062400008