RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates
Research output: Contribution to journal › Journal article › Research › peer-review
Plasticity of cells, tissues, and organs is controlled by the coordinated transcription of biological programs. However, the mechanisms orchestrating such context-specific transcriptional networks mediated by the dynamic interplay of transcription factors and coregulators are poorly understood. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a prototypical master regulator of adaptive transcription in various cell types. We now uncovered a central function of the C-terminal domain of PGC-1α to bind RNAs and assemble multiprotein complexes including proteins that control gene transcription and RNA processing. These interactions are important for PGC-1α recruitment to chromatin in transcriptionally active liquid-like nuclear condensates. Notably, such a compartmentalization of active transcription mediated by liquid-liquid phase separation was observed in mouse and human skeletal muscle, revealing a mechanism by which PGC-1α regulates complex transcriptional networks. These findings provide a broad conceptual framework for context-dependent transcriptional control of phenotypic adaptations in metabolically active tissues.
Original language | English |
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Article number | e2105951118 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 118 |
Issue number | 36 |
Number of pages | 11 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 2021 |
- Faculty of Science - Gene transcription, Transcriptional coactivator, Chromatin, Liquid-liquid phase separation, RNA-binding protein
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433555/pdf/pnas.202105951.pdf
Final published version
ID: 278486209