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<p>Transcription factors play a key role in regulating gene expression. We conduct an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training to identify coordinated epigenomic and transcriptional changes and determine key transcription factors involved. We uncover tissue-specific endurance exercise training associated changes and transcription factor motif enrichment across differentially expressed genes, accessible regions, and methylated regions. We discover distinct routes of training-induced regulation through either epigenomic alterations providing better access for transcription factors to affect target genes, or via changes in transcription factor expression or activity enabling target gene responses. We identify transcription factor motifs enriched among correlated epigenomic and transcriptomic alterations, differentially expressed genes correlated with exercise-related phenotypic and cell type composition changes, and training-induced activity changes of transcription factors whose target genes are enriched for differentially expressed genes. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to training across tissues.</p>

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Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月21日

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  • Gregory R. Smith,
  • Bingqing Zhao,
  • Malene E. Lindholm,
  • Archana Raja,
  • Mark Viggars,
  • Hanna Pincas,
  • Nicole R. Gay,
  • Yifei Sun,
  • Sindhu Vangeti,
  • Yongchao Ge,
  • Venugopalan D. Nair,
  • James A. Sanford,
  • Mary Anne S. Amper,
  • Mital Vasoya,
  • Kevin S. Smith,
  • Irene Ramos,
  • Stephen B. Montgomery,
  • Elena Zaslavsky,
  • Sue C. Bodine,
  • Karyn A. Esser,
  • Martin J. Walsh,
  • Michael P. Snyder,
  • Stuart C. Sealfon,
  • Joshua N. Adkins,
  • Brent G. Albertson,
  • David Amar,
  • Mary Anne S. Amper,
  • Jose Juan Almagro Armenteros,
  • Euan Ashley,
  • Julian Avila-Pacheco,
  • Dam Bae,
  • Ali Tugrul Balci,
  • Marcas Bamman,
  • Nasim Bararpour,
  • Elisabeth R. Barton,
  • Pierre M. Jean Beltran,
  • Bryan C. Bergman,
  • Daniel H. Bessesen,
  • Sue C. Bodine,
  • Frank W. Booth,
  • Brian Bouverat,
  • Thomas W. Buford,
  • Charles F. Burant,
  • Tiziana Caputo,
  • Steven Carr,
  • Toby L. Chambers,
  • Clarisa Chavez,
  • Maria Chikina,
  • Roxanne Chiu,
  • Michael Cicha,
  • Clary B. Clish,
  • Paul M. Coen,
  • Dan Cooper,
  • Elaine Cornell,
  • Gary Cutter,
  • Karen P. Dalton,
  • Surendra Dasari,
  • Courtney Dennis,
  • Karyn Esser,
  • Charles R. Evans,
  • Roger Farrar,
  • Facundo M. Fernández,
  • Kishore Gadde,
  • Nicole Gagne,
  • David A. Gaul,
  • Nicole R. Gay,
  • Yongchao Ge,
  • Robert E. Gerszten,
  • Bret H. Goodpaster,
  • Laurie J. Goodyear,
  • Marina A. Gritsenko,
  • Kristy Guevara,
  • Fadia Haddad,
  • Joshua R. Hansen,
  • Melissa Harris,
  • Trevor Hastie,
  • Krista M. Hennig,
  • Steven G. Hershman,
  • Andrea Hevener,
  • Michael F. Hirshman,
  • Zhenxin Hou,
  • Fang-Chi Hsu,
  • Kim M. Huffman,
  • Chia-Jui Hung,
  • Chelsea Hutchinson-Bunch,
  • Anna A. Ivanova,
  • Bailey E. Jackson,
  • Catherine M. Jankowski,
  • David Jimenez-Morales,
  • Christopher A. Jin,
  • Neil M. Johannsen,
  • Robert L. Newton Jr,
  • Maureen T. Kachman,
  • Benjamin G. Ke,
  • Hasmik Keshishian,
  • Wendy M. Kohrt,
  • Kyle S. Kramer,
  • William E. Kraus,
  • Ian Lanza,
  • Christiaan Leeuwenburgh,
  • Sarah J. Lessard,
  • Bridget Lester,
  • Jun Z. Li,
  • Malene E. Lindholm,
  • Ana K. Lira,
  • Xueyun Liu,
  • Ching-ju Lu,
  • Nathan S. Makarewicz,
  • Kristal M. Maner-Smith,
  • D. R. Mani,
  • Gina M. Many,
  • Nada Marjanovic,
  • Andrea Marshall,
  • Shruti Marwaha,
  • Sandy May,
  • Edward L. Melanson,
  • Michael E. Miller,
  • Matthew E. Monroe,
  • Stephen B. Montgomery,
  • Samuel G. Moore,
  • Ronald J. Moore,
  • Kerrie L. Moreau,
  • Charles C. Mundorff,
  • Nicolas Musi,
  • Daniel Nachun,
  • Venugopalan D. Nair,
  • K. Sreekumaran Nair,
  • Michael D. Nestor,
  • Barbara Nicklas,
  • Pasquale Nigro,
  • German Nudelman,
  • Eric A. Ortlund,
  • Marco Pahor,
  • Cadence Pearce,
  • Vladislav A. Petyuk,
  • Paul D. Piehowski,
  • Hanna Pincas,
  • Scott Powers,
  • David M. Presby,
  • Wei-Jun Qian,
  • Shlomit Radom-Aizik,
  • Archana Natarajan Raja,
  • Krithika Ramachandran,
  • Megan E. Ramaker,
  • Irene Ramos,
  • Tuomo Rankinen,
  • Alexander Sasha Raskind,
  • Blake B. Rasmussen,
  • Eric Ravussin,
  • R. Scott Rector,
  • W. Jack Rejeski,
  • Collyn Z-T. Richards,
  • Stas Rirak,
  • Jeremy M. Robbins,
  • Jessica L. Rooney,
  • Aliza B. Rubenstein,
  • Frederique Ruf-Zamojski,
  • Scott Rushing,
  • Tyler J. Sagendorf,
  • Mihir Samdarshi,
  • Evan M. Savage,
  • Irene E. Schauer,
  • Simon Schenk,
  • Robert S. Schwartz,
  • Stuart C. Sealfon,
  • Nitish Seenarine,
  • Kevin S. Smith,
  • Michael P. Snyder,
  • Tanu Soni,
  • Luis Gustavo Oliveira De Sousa,
  • Lauren M. Sparks,
  • Alec Steep,
  • Cynthia L. Stowe,
  • Yifei Sun,
  • Christopher Teng,
  • Anna Thalacker-Mercer,
  • John Thyfault,
  • Rob Tibshirani,
  • Russell Tracy,
  • Scott Trappe,
  • Todd A. Trappe,
  • Karan Uppal,
  • Sindhu Vangeti,
  • Mital Vasoya,
  • Nikolai G. Vetr,
  • Elena Volpi,
  • Alexandria Vornholt,
  • Michael P. Walkup,
  • Martin J. Walsh,
  • Matthew T. Wheeler,
  • John P. Williams,
  • Si Wu,
  • Ashley Xia,
  • Zhen Yan,
  • Xuechen Yu,
  • Chongzhi Zang,
  • Elena Zaslavsky,
  • Navid Zebarjadi,
  • Tiantian Zhang,
  • Jimmy Zhen

摘要

Transcription factors play a key role in regulating gene expression. We conduct an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training to identify coordinated epigenomic and transcriptional changes and determine key transcription factors involved. We uncover tissue-specific endurance exercise training associated changes and transcription factor motif enrichment across differentially expressed genes, accessible regions, and methylated regions. We discover distinct routes of training-induced regulation through either epigenomic alterations providing better access for transcription factors to affect target genes, or via changes in transcription factor expression or activity enabling target gene responses. We identify transcription factor motifs enriched among correlated epigenomic and transcriptomic alterations, differentially expressed genes correlated with exercise-related phenotypic and cell type composition changes, and training-induced activity changes of transcription factors whose target genes are enriched for differentially expressed genes. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to training across tissues.