Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility
| Autor: | Vikas Soni, Grégory Fettweis, Thomas A. Johnson, Diego M. Presman, Prabhakar R. Gudla, Anh Huynh, Gianluca Pegoraro, David A. Garcia, George Zaki, Diana A. Stavreva, Geneva Williams, R. Louis Schiltz, Matthew L. Ferguson, Andrew McGowan, Gordon L. Hager, Murali Palangat, Arpita Upadhyaya |
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| Rok vydání: | 2018 |
| Předmět: |
Transcription
Genetic medicine.medical_treatment Stimulation Biology Article 03 medical and health sciences Bursting Mice 0302 clinical medicine Glucocorticoid receptor Receptors Glucocorticoid Transcription (biology) medicine Animals Promoter Regions Genetic Molecular Biology Transcription factor Glucocorticoids 030304 developmental biology Transcriptional bursting 0303 health sciences RNA Cell Biology Cell biology Steroid hormone Transcription Initiation Site 030217 neurology & neurosurgery |
| Zdroj: | Mol Cell |
| ISSN: | 1097-4164 |
| Popis: | Genes are transcribed in a discontinuous pattern referred to as RNA bursting, but the mechanisms regulating this process are unclear. Although many physiological signals, including glucocorticoid hormones, are pulsatile, the effects of transient stimulation on bursting are unknown. Here we characterize RNA synthesis from single-copy glucocorticoid receptor (GR)-regulated transcription sites (TSs) under pulsed (ultradian) and constant hormone stimulation. In contrast to constant stimulation, pulsed stimulation induces restricted bursting centered around the hormonal pulse. Moreover, we demonstrate that transcription factor (TF) nuclear mobility determines burst duration, whereas its bound fraction determines burst frequency. Using 3D tracking of TSs, we directly correlate TF binding and RNA synthesis at a specific promoter. Finally, we uncover a striking co-bursting pattern between TSs located at proximal and distal positions in the nucleus. Together, our data reveal a dynamic interplay between TF mobility and RNA bursting that is responsive to stimuli strength, type, modality, and duration. |
| Databáze: | OpenAIRE |
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