Evidence map›Paper›PMID 41957025›Full record

ArticleNature communications2026

BRD4 directs myofiber identity and metabolic adaptation through CHD4 cooperation.

Zheng Zhou, Lin Liu, Zhisheng Xu, Danxia Zhou, Anqi Liu, Jiachen Yuan, Gonghao Shen, Qiqi Guo, Yujing Yin, Yan Mao and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

21 authors.

Zheng Zhou *State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.ORCID 0000-0002-9000-9046
Lin Liu *Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9087-1146
Zhisheng Xu *State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Danxia ZhouState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Anqi LiuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Jiachen YuanState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Gonghao ShenState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Qiqi GuoState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Yujing YinState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Yan MaoState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.ORCID 0000-0003-0782-4611
Wanping SunState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Liwei XiaoState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Cheng LvDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Abdukahar KiramState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Likun YangState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Yuhuan JiaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.
Lu KeDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-8093-5073
Lei FangJiangsu Key Laboratory of Molecular Medicine & Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, China.ORCID 0000-0002-2582-4845
Weiqin LiDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Tingting FuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China.ORCID 0000-0002-5538-1117
Zhenji GanState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Medical School of Nanjing University, Nanjing University, Nanjing, China. ganzj@nju.edu.cn.ORCID 0000-0001-5940-207X

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2022YFA0806000National Natural Science Foundation of China (National Science Foundation of China) 31922033National Natural Science Foundation of China (National Science Foundation of China) 32071136National Natural Science Foundation of China (National Science Foundation of China) 32300970National Natural Science Foundation of China (National Science Foundation of China) 32471226National Natural Science Foundation of China (National Science Foundation of China) 91857105National Natural Science Foundation of China (National Science Foundation of China) 92457302
6 · The paper itself

Abstract

Skeletal muscle fiber-type composition is key determinant of systemic metabolism and health. However, how fiber-type-specific gene expression patterns are established and maintained to specify myofiber identity remains unclear. Here we show that BRD4 is a crucial regulator for muscle fiber identity and metabolism. In humans, BRD4 expression correlates with muscle contractile properties, and is notably altered in individuals with obesity. In mice, HFD feeding elevates BRD4 protein levels, preceding body weight changes, while muscle-specific Brd4 deletion induces a slow-oxidative fiber shift, enhances energy expenditure, and protects against diet-induced obesity and insulin resistance. Mechanistically, BRD4 cooperates with MEF2 and CHD4 to regulate fast-twitch myofiber gene expression. CHD4 deletion mirrors the metabolic benefits seen with BRD4 loss. Importantly, BRD4 inhibition with JQ1 replicates these effects in mice and human myotubes. These findings establish BRD4 axis as a critical determinant of myofiber identity and metabolism, offering a potential therapeutic strategy for metabolic disorders.

Indexed as

Cell Cycle ProteinsMuscle Fibers, SkeletalNuclear ProteinsTranscription FactorsAnimalsAzepinesBromodomain Containing ProteinsDiet, High-FatEnergy MetabolismFemaleHumansInsulin ResistanceMaleMEF2 Transcription FactorsMiceMice, Inbred C57BLAzepinesBRD4 protein, humanBrd4 protein, mouseBromodomain Containing ProteinsCell Cycle Proteins(+)-JQ1 compoundMEF2 Transcription FactorsNuclear ProteinsTranscription FactorsTriazoles

Identifiers

PMID41957025
PMCPMC13223318

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