The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

Sebastian Edman; Ronald G Jones Iii; Paulo R Jannig; Rodrigo Fernandez-Gonzalo; Jessica Norrbom; Nicholas T Thomas; Sabin Khadgi; Pieter J Koopmans; Francielly Morena; Toby L Chambers; Calvin S Peterson; Logan N Scott; Nicholas P Greene; Vandre C Figueiredo; Christopher S Fry; Liu Zhengye; Johanna T Lanner; Yuan Wen; Björn Alkner; Kevin A Murach; Ferdinand von Walden

doi:10.1038/s44319-024-00299-z

The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

Sebastian Edman, Ronald G Jones Iii, Paulo R Jannig, Rodrigo Fernandez-Gonzalo, Jessica Norrbom, Nicholas T Thomas, Sabin Khadgi, Pieter J Koopmans, Francielly Morena, Toby L Chambers, Calvin S Peterson, Logan N Scott, Nicholas P Greene, Vandre C Figueiredo, Christopher S Fry, Liu Zhengye, Johanna T Lanner, Yuan Wen, Björn Alkner, Kevin A MurachFerdinand von Walden

Research output: Contribution to journal › Article › peer-review

Abstract

A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle ( http://data.myoanalytics.com ) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape.

Original language	English
Pages (from-to)	5810-5837
Number of pages	28
Journal	EMBO Reports
Volume	25
Issue number	12
DOIs	https://doi.org/10.1038/s44319-024-00299-z
State	Published - Dec 2024

Bibliographical note

Keywords

Humans
Muscle, Skeletal/metabolism
Proto-Oncogene Proteins c-myc/genetics
Animals
Mice
Exercise/physiology
Male
Adult
DNA Methylation
Gene Expression Regulation
Muscle Development/genetics

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10.1038/s44319-024-00299-z

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Edman, S., Jones Iii, R. G., Jannig, P. R., Fernandez-Gonzalo, R., Norrbom, J., Thomas, N. T., Khadgi, S., Koopmans, P. J., Morena, F., Chambers, T. L., Peterson, C. S., Scott, L. N., Greene, N. P., Figueiredo, V. C., Fry, C. S., Zhengye, L., Lanner, J. T., Wen, Y., Alkner, B., ... von Walden, F. (2024). The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth. EMBO Reports, 25(12), 5810-5837. https://doi.org/10.1038/s44319-024-00299-z

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title = "The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth",

abstract = "A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle ( http://data.myoanalytics.com ) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape.",

keywords = "Humans, Muscle, Skeletal/metabolism, Proto-Oncogene Proteins c-myc/genetics, Animals, Mice, Exercise/physiology, Male, Adult, DNA Methylation, Gene Expression Regulation, Muscle Development/genetics",

author = "Sebastian Edman and {Jones Iii}, {Ronald G} and Jannig, {Paulo R} and Rodrigo Fernandez-Gonzalo and Jessica Norrbom and Thomas, {Nicholas T} and Sabin Khadgi and Koopmans, {Pieter J} and Francielly Morena and Chambers, {Toby L} and Peterson, {Calvin S} and Scott, {Logan N} and Greene, {Nicholas P} and Figueiredo, {Vandre C} and Fry, {Christopher S} and Liu Zhengye and Lanner, {Johanna T} and Yuan Wen and Bj{\"o}rn Alkner and Murach, {Kevin A} and {von Walden}, Ferdinand",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s44319-024-00299-z",

language = "English",

volume = "25",

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Edman, S, Jones Iii, RG, Jannig, PR, Fernandez-Gonzalo, R, Norrbom, J, Thomas, NT, Khadgi, S, Koopmans, PJ, Morena, F, Chambers, TL, Peterson, CS, Scott, LN, Greene, NP, Figueiredo, VC, Fry, CS, Zhengye, L, Lanner, JT, Wen, Y, Alkner, B, Murach, KA & von Walden, F 2024, 'The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth', EMBO Reports, vol. 25, no. 12, pp. 5810-5837. https://doi.org/10.1038/s44319-024-00299-z

TY - JOUR

T1 - The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

AU - Edman, Sebastian

AU - Jones Iii, Ronald G

AU - Jannig, Paulo R

AU - Fernandez-Gonzalo, Rodrigo

AU - Norrbom, Jessica

AU - Thomas, Nicholas T

AU - Khadgi, Sabin

AU - Koopmans, Pieter J

AU - Morena, Francielly

AU - Chambers, Toby L

AU - Peterson, Calvin S

AU - Scott, Logan N

AU - Greene, Nicholas P

AU - Figueiredo, Vandre C

AU - Fry, Christopher S

AU - Zhengye, Liu

AU - Lanner, Johanna T

AU - Wen, Yuan

AU - Alkner, Björn

AU - Murach, Kevin A

AU - von Walden, Ferdinand

PY - 2024/12

Y1 - 2024/12

N2 - A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle ( http://data.myoanalytics.com ) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape.

AB - A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle ( http://data.myoanalytics.com ) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape.

KW - Humans

KW - Muscle, Skeletal/metabolism

KW - Proto-Oncogene Proteins c-myc/genetics

KW - Animals

KW - Mice

KW - Exercise/physiology

KW - Male

KW - Adult

KW - DNA Methylation

KW - Gene Expression Regulation

KW - Muscle Development/genetics

U2 - 10.1038/s44319-024-00299-z

DO - 10.1038/s44319-024-00299-z

M3 - Article

C2 - 39482487

SN - 1469-221X

VL - 25

SP - 5810

EP - 5837

JO - EMBO Reports

JF - EMBO Reports

IS - 12

ER -

The 24-hour molecular landscape after exercise in humans reveals MYC is sufficient for muscle growth

Abstract

Bibliographical note

Keywords

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