| First Author | Hodge BA | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 30789342 | Mgi Jnum | J:275130 |
| Mgi Id | MGI:6304160 | Doi | 10.7554/eLife.43017 |
| Citation | Hodge BA, et al. (2019) MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle. Elife 8:e43017 |
| abstractText | In the present study we show that the master myogenic regulatory factor, MYOD1, is a positive modulator of molecular clock amplitude and functions with the core clock factors for expression of clock-controlled genes in skeletal muscle. We demonstrate that MYOD1 directly regulates the expression and circadian amplitude of the positive core clock factor Bmal1. We identify a non-canonical E-box element in Bmal1 and demonstrate that is required for full MYOD1-responsiveness. Bimolecular fluorescence complementation assays demonstrate that MYOD1 colocalizes with both BMAL1 and CLOCK throughout myonuclei. We demonstrate that MYOD1 and BMAL1:CLOCK work in a synergistic fashion through a tandem E-box to regulate the expression and amplitude of the muscle specific clock-controlled gene, Titin-cap (Tcap). In conclusion, these findings reveal mechanistic roles for the muscle specific transcription factor MYOD1 in the regulation of molecular clock amplitude as well as synergistic regulation of clock-controlled genes in skeletal muscle. |
