p53 mediates target gene association with nuclear speckles for amplified RNA expression
| Autor: | Omid Gholamalamdari, Shawn C. Little, K.M.A. Tanim, Charly R. Good, Joan Lim, Andrew S. Belmont, Margaret C. Dunagin, Liguo Zhang, Katherine A. Alexander, Son C. Nguyen, Paula Agudelo-Garcia, Enrique Lin-Shiao, Allison Cote, Mariel R. Mendoza, Eric F. Joyce, Nicolas Biddle, Shelley L. Berger, Arjun Raj |
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| Rok vydání: | 2021 |
| Předmět: |
Transcriptional Activation
Transcription Genetic Intranuclear Inclusion Bodies Biology Article 03 medical and health sciences Speckle pattern Transactivation 0302 clinical medicine Transcription (biology) Gene expression Humans Molecular Biology Gene Transcription factor 030304 developmental biology Cell Nucleus Regulation of gene expression 0303 health sciences Nuclear Proteins RNA DNA Cell Biology Cell biology HEK293 Cells Gene Expression Regulation Tumor Suppressor Protein p53 030217 neurology & neurosurgery Protein Binding Transcription Factors |
| Zdroj: | Mol Cell |
| ISSN: | 1097-2765 |
| Popis: | Nuclear speckles are prominent nuclear bodies that contain proteins and RNA involved in gene expression. While links between nuclear speckles and gene activation are emerging, the mechanisms regulating association of genes with speckles are unclear. We find that speckle association of p53 target genes is driven by the p53 transcription factor. Focusing on p21, a key p53 target, we demonstrate that speckle association boosts expression by elevating nascent RNA amounts. p53-regulated speckle association did not depend on p53 transactivation functions, but required an intact proline-rich domain and direct DNA binding, providing mechanisms within p53 for regulating gene-speckle association. Beyond p21, a substantial subset of p53 targets have p53-regulated speckle association. Strikingly, speckle-associating p53 targets are more robustly activated and occupy a distinct niche of p53 biology compared to non-speckle-associating p53 targets. Together, our findings illuminate regulated speckle association as a mechanism utilized by a transcription factor to boost gene expression. |
| Databáze: | OpenAIRE |
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