MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle

ELife
Brian A HodgeKaryn A Esser

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.

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Citations

Jul 31, 2019·American Journal of Physiology. Endocrinology and Metabolism·Michael L RossettiBradley S Gordon
Nov 27, 2019·Nature Reviews. Molecular Cell Biology·Alina PatkeSofia Axelrod
Jun 17, 2020·The Journal of Physiology·Denise KemlerKaryn A Esser
Aug 5, 2020·FEBS Letters·Anna-Marie FingerAchim Kramer
May 30, 2020·Obesity·Miguel A Gutierrez-MonrealKaryn A Esser
Jan 24, 2020·Journal of Animal Science and Biotechnology·Emilio Mármol-SánchezMarcel Amills
Dec 17, 2020·Physiology·Collin M DouglasKaryn A Esser
Jan 6, 2021·Annals of the Rheumatic Diseases·Honor MorrisQing-Jun Meng
Jan 31, 2020·Journal of Molecular Biology·Flore SinturelCharna Dibner
Jan 17, 2020·Journal of Molecular Biology·Carrie L Partch
May 4, 2021·Frontiers in Neuroscience·Shinya AoyamaKazuyuki Shinohara
Apr 25, 2021·The European Journal of Neuroscience·Christina L RubyRobert D Hinrichsen
May 20, 2021·The Journal of Cell Biology·Nobuko Katoku-KikyoNobuaki Kikyo
Sep 21, 2021·American Journal of Physiology. Endocrinology and Metabolism·Abigail L TiceJennifer L Steiner

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Datasets Mentioned

BETA
GSE122082

Methods Mentioned

BETA
ChIP-Seq
transfection
fluorescence complementation assay
ChIP-PCR
pulldowns
PCR
ChIP
immunoprecipitation
pull-down

Software Mentioned

package
CYCLE
HOMER
Trimmomatic
Tcap
Actimetrix
FastQ Groomer
findGO
R
makeTagDirectory

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