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Genome-wide analyses in neuronal cells reveal that upstream transcription factors regulate lysosomal gene expression
- Source :
- The FEBS journal. 283(6)
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Male
Leucine zipper
Chromatin Immunoprecipitation
USF2
USF1
Biochemistry
Cell Line
E-Box Elements
03 medical and health sciences
Mice
0302 clinical medicine
Gene expression
Animals
Promoter Regions, Genetic
Molecular Biology
Gene
Transcription factor
Oligonucleotide Array Sequence Analysis
Cerebral Cortex
Neurons
Gene knockdown
Binding Sites
biology
Cell Biology
Molecular biology
030104 developmental biology
Gene Expression Regulation
Gene Knockdown Techniques
biology.protein
Mice, Inbred CBA
Upstream Stimulatory Factors
Lysosomes
Chromatin immunoprecipitation
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 17424658
- Volume :
- 283
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The FEBS journal
- Accession number :
- edsair.doi.dedup.....c2d116bedf4ab60752c2cb11396c2632