MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle
- University of Florida, United States
- Genentech Inc, United States
- Allen Institute for Brain Science, United States
Abstract
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.
Data availability
ChIP seq data for muscle with MyoD is deposited in GEO under accession code GSE122082.
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MyoD ChIPseq and skeletal muscle tissueNCBI Gene Expression Omnibus, GSE122082.
Article and author information
Author details
Funding
National Institutes of Health (R01AR066082)
- Karyn A Esser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (IACUC Study 201809136) of the University of Florida.
Reviewing Editor
- Andrew Brack, University of California, San Francisco, United States
Version history
- Received: October 19, 2018
- Accepted: February 20, 2019
- Accepted Manuscript published: February 21, 2019 (version 1)
- Version of Record published: March 4, 2019 (version 2)
Copyright
© 2019, Hodge et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle
eLife 8:e43017.
https://doi.org/10.7554/eLife.43017
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