Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y
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 differen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78682-8 |
| _version_ | 1818840863456886784 |
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| author | Tomoyuki Yamanaka Haruko Miyazaki Asako Tosaki Sankar N. Maity Tomomi Shimogori Nobutaka Hattori Nobuyuki Nukina |
| author_facet | Tomoyuki Yamanaka Haruko Miyazaki Asako Tosaki Sankar N. Maity Tomomi Shimogori Nobutaka Hattori Nobuyuki Nukina |
| author_sort | Tomoyuki Yamanaka |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T04:16:57Z |
| format | Article |
| id | doaj.art-ccbc7ee531b049c7937f687cdc397d5f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:16:57Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ccbc7ee531b049c7937f687cdc397d5f2022-12-21T20:36:17ZengNature PortfolioScientific Reports2045-23222020-12-0110111410.1038/s41598-020-78682-8Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-YTomoyuki Yamanaka0Haruko Miyazaki1Asako Tosaki2Sankar N. Maity3Tomomi Shimogori4Nobutaka Hattori5Nobuyuki Nukina6Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain ScienceLaboratory of Structural Neuropathology, Doshisha University Graduate School of Brain ScienceLaboratory for Structural Neuropathology, RIKEN Brain Science InstituteDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterLaboratory for Molecular Mechanisms of Brain Development, RIKEN Center for Brain ScienceDepartment of Neurology, Juntendo University Graduate School of MedicineLaboratory of Structural Neuropathology, Doshisha University Graduate School of Brain ScienceAbstract 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.https://doi.org/10.1038/s41598-020-78682-8 |
| spellingShingle | Tomoyuki Yamanaka Haruko Miyazaki Asako Tosaki Sankar N. Maity Tomomi Shimogori Nobutaka Hattori Nobuyuki Nukina Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y Scientific Reports |
| title | Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y |
| title_full | Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y |
| title_fullStr | Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y |
| title_full_unstemmed | Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y |
| title_short | Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y |
| title_sort | gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by nf y |
| url | https://doi.org/10.1038/s41598-020-78682-8 |
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