IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35070-2.html
   My bibliography  Save this article

DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal

Author

Listed:
  • Paola Cattaneo

    (University of California San Diego
    Milan Unit, National Research Council of Italy
    Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main)

  • Michael G. B. Hayes

    (University of California San Diego)

  • Nina Baumgarten

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main)

  • Dennis Hecker

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main)

  • Sofia Peruzzo

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt)

  • Galip S. Aslan

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt
    Goethe University)

  • Paolo Kunderfranco

    (IRCCS Humanitas Research Hospital)

  • Veronica Larcher

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt)

  • Lunfeng Zhang

    (University of California San Diego)

  • Riccardo Contu

    (University of California San Diego)

  • Gregory Fonseca

    (McGill University)

  • Simone Spinozzi

    (University of California San Diego)

  • Ju Chen

    (University of California San Diego)

  • Gianluigi Condorelli

    (Milan Unit, National Research Council of Italy
    IRCCS Humanitas Research Hospital
    Humanitas University)

  • Stefanie Dimmeler

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt)

  • Marcel H. Schulz

    (Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt)

  • Sven Heinz

    (University of California San Diego)

  • Nuno Guimarães-Camboa

    (University of California San Diego
    Goethe University
    German Center for Cardiovascular Research (DZHK), Partner Site Rhein Main
    Goethe University Frankfurt)

  • Sylvia M. Evans

    (University of California San Diego
    University of California San Diego)

Abstract

Mechanisms by which specific histone modifications regulate distinct gene networks remain little understood. We investigated how H3K79me2, a modification catalyzed by DOT1L and previously considered a general transcriptional activation mark, regulates gene expression during cardiogenesis. Embryonic cardiomyocyte ablation of Dot1l revealed that H3K79me2 does not act as a general transcriptional activator, but rather regulates highly specific transcriptional networks at two critical cardiogenic junctures: embryonic cardiogenesis, where it was particularly important for left ventricle-specific genes, and postnatal cardiomyocyte cell cycle withdrawal, with Dot1L mutants having more mononuclear cardiomyocytes and prolonged cardiomyocyte cell cycle activity. Mechanistic analyses revealed that H3K79me2 in two distinct domains, gene bodies and regulatory elements, synergized to promote expression of genes activated by DOT1L. Surprisingly, H3K79me2 in specific regulatory elements also contributed to silencing genes usually not expressed in cardiomyocytes. These results reveal mechanisms by which DOT1L successively regulates left ventricle specification and cardiomyocyte cell cycle withdrawal.

Suggested Citation

  • Paola Cattaneo & Michael G. B. Hayes & Nina Baumgarten & Dennis Hecker & Sofia Peruzzo & Galip S. Aslan & Paolo Kunderfranco & Veronica Larcher & Lunfeng Zhang & Riccardo Contu & Gregory Fonseca & Sim, 2022. "DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35070-2
    DOI: 10.1038/s41467-022-35070-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35070-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35070-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
    3. Laura Godfrey & Nicholas T. Crump & Ross Thorne & I-Jun Lau & Emmanouela Repapi & Dimitra Dimou & Alastair L. Smith & Joe R. Harman & Jelena M. Telenius & A. Marieke Oudelaar & Damien J. Downes & Pare, 2019. "DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Joschka Hey & Michelle Paulsen & Reka Toth & Dieter Weichenhan & Simone Butz & Jolanthe Schatterny & Reinhard Liebers & Pavlo Lutsik & Christoph Plass & Marcus A. Mall, 2021. "Epigenetic reprogramming of airway macrophages promotes polarization and inflammation in muco-obstructive lung disease," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Congcong Tian & Jiaqi Zhou & Xinran Li & Yuan Gao & Qing Wen & Xing Kang & Nan Wang & Yuan Yao & Jiuhang Jiang & Guibing Song & Tianjun Zhang & Suili Hu & JingYi Liao & Chuanhe Yu & Zhiquan Wang & Xia, 2023. "Impaired histone inheritance promotes tumor progression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Xiaomei Zhang & Lihao Ge & Guanghui Jin & Yasong Liu & Qingfen Yu & Weizhao Chen & Liang Chen & Tao Dong & Kiyoharu J. Miyagishima & Juan Shen & Jinghong Yang & Guo Lv & Yan Xu & Qing Yang & Linsen Ye, 2024. "Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Siobhan Rice & Thomas Jackson & Nicholas T. Crump & Nicholas Fordham & Natalina Elliott & Sorcha O’Byrne & Maria del Mar Lara Fanego & Dilys Addy & Trisevgeni Crabb & Carryl Dryden & Sarah Inglott & D, 2021. "A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    7. Nickole Moon & Christopher P. Morgan & Ruth Marx-Rattner & Alyssa Jeng & Rachel L. Johnson & Ijeoma Chikezie & Carmen Mannella & Mary D. Sammel & C. Neill Epperson & Tracy L. Bale, 2024. "Stress increases sperm respiration and motility in mice and men," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    11. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Yawen Lei & Yaoguang Yu & Wei Fu & Tao Zhu & Caihong Wu & Zhihao Zhang & Zewang Yu & Xin Song & Jianqu Xu & Zhenwei Liang & Peitao Lü & Chenlong Li, 2024. "BCL7A and BCL7B potentiate SWI/SNF-complex-mediated chromatin accessibility to regulate gene expression and vegetative phase transition in plants," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    13. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    14. Tianshi Feng & Xuemei Zhao & Ping Gu & Wah Yang & Cunchuan Wang & Qingyu Guo & Qiaoyun Long & Qing Liu & Ying Cheng & Jin Li & Cynthia Kwan Yui Cheung & Donghai Wu & Xinyu Kong & Yong Xu & Dewei Ye & , 2022. "Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Elisa Bellucci & Andrea Benazzo & Chunming Xu & Elena Bitocchi & Monica Rodriguez & Saleh Alseekh & Valerio Di Vittori & Tania Gioia & Kerstin Neumann & Gaia Cortinovis & Giulia Frascarelli & Ester Mu, 2023. "Selection and adaptive introgression guided the complex evolutionary history of the European common bean," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Jiayin Peng & Lili Han & Biao Liu & Jiawen Song & Yuang Wang & Kunpeng Wang & Qian Guo & XinYan Liu & Yu Li & Jujin Zhang & Wenqing Wu & Sheng Li & Xin Fu & Cheng-le Zhuang & Weikang Zhang & Shengbao , 2023. "Gli1 marks a sentinel muscle stem cell population for muscle regeneration," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    17. Brent S. Perlman & Noah Burget & Yeqiao Zhou & Gregory W. Schwartz & Jelena Petrovic & Zora Modrusan & Robert B. Faryabi, 2024. "Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    18. Elisa Setten & Alessandra Castagna & Josué Manik Nava-Sedeño & Jonathan Weber & Roberta Carriero & Andreas Reppas & Valery Volk & Jessica Schmitz & Wilfried Gwinner & Haralampos Hatzikirou & Friedrich, 2022. "Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    19. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35070-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.