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Genome‐wide analyses in neuronal cells reveal that upstream transcription factors regulate lysosomal gene expression
Author(s) -
Yamanaka Tomoyuki,
Tosaki Asako,
Kurosawa Masaru,
Shimogori Tomomi,
Hattori Nobutaka,
Nukiobuyuki
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13650
Subject(s) - chromatin immunoprecipitation , biology , gene knockdown , gene expression , gene , transcription factor , microbiology and biotechnology , regulation of gene expression , transcription (linguistics) , promoter , genetics , linguistics , philosophy
The upstream transcription factors ( USF s) USF 1 and USF 2 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 USF 1 from mouse brain cortex. Subsequent promoter array analysis (Ch IP ‐chip) indicated that USF 1 exclusively bound to the CACGTG E‐box motifs in the proximal promoter regions. Importantly, functional annotation of the USF 1‐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 USF s de‐regulated lysosomal gene expression. Altered expression was validated by quantitative RT ‐ PCR , supporting the conclusion that USF s regulate lysosomal gene expression. Furthermore, USF knockdown slightly increased LysoTracker Red staining, implying a role for USF s in modulating lysosomal homeostasis. Together, our comprehensive genome‐scale analyses identified lysosomal genes as targets of USF s in neuronal cells, suggesting a potential additional pathway of lysosomal regulation. Database The data for the gene expression array and Ch IP ‐chip have been submitted to the Gene Expression Omnibus ( GEO ) under accession numbers GSE76615 and GSE76616 , respectively.