1. Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y
- Author
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Tomoyuki Yamanaka, Nobuyuki Nukina, Asako Tosaki, Nobutaka Hattori, Tomomi Shimogori, Sankar N. Maity, and Haruko Miyazaki
- Subjects
Therapeutic gene modulation ,RNA Splicing ,Science ,Biology ,Endoplasmic Reticulum ,Article ,Transcriptome ,Mice ,Gene expression analysis ,Sequencing ,Animals ,Homeostasis ,Humans ,Transcriptomics ,Gene ,Organelles ,Neurons ,Multidisciplinary ,Gene Expression Profiling ,Cell Cycle ,Alternative splicing ,Promoter ,Embryonic stem cell ,Cellular neuroscience ,Cell biology ,Gene expression profiling ,Alternative Splicing ,CCAAT-Binding Factor ,Medicine ,Transcription ,Chromatin immunoprecipitation ,HeLa Cells - Abstract
A heterotrimeric transcription factor NF-Y is crucial for cell-cycle progression in various types of cells. In contrast, studies using NF-YA knockout mice have unveiled its essential role in endoplasmic reticulum (ER) homeostasis in neuronal cells. However, whether NF-Y modulates a different transcriptome to mediate distinct cellular functions remains obscure. Here, we knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and mouse brain striatal cells, and performed gene expression profiling. We found that down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. This contrasts with the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that the transcriptomic difference was not correlated with DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration could be involved in this cell type-specific gene modulation.
- Published
- 2020