IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29142-6.html
   My bibliography  Save this article

Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia

Author

Listed:
  • Moritz Binder

    (Mayo Clinic
    Mayo Clinic)

  • Ryan M. Carr

    (Mayo Clinic)

  • Terra L. Lasho

    (Mayo Clinic)

  • Christy M. Finke

    (Mayo Clinic)

  • Abhishek A. Mangaonkar

    (Mayo Clinic)

  • Christopher L. Pin

    (University of Western Ontario)

  • Kurt R. Berger

    (University of Western Ontario)

  • Amelia Mazzone

    (Mayo Clinic
    Mayo Clinic)

  • Sandeep Potluri

    (University of Birmingham)

  • Tamas Ordog

    (Mayo Clinic)

  • Keith D. Robertson

    (Mayo Clinic)

  • David L. Marks

    (Mayo Clinic)

  • Martin E. Fernandez-Zapico

    (Mayo Clinic)

  • Alexandre Gaspar-Maia

    (Mayo Clinic
    Mayo Clinic)

  • Mrinal M. Patnaik

    (Mayo Clinic
    Mayo Clinic)

Abstract

Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. Truncating mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic resistance, and poor survival outcomes. We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1MT in chronic myelomonocytic leukemia (CMML). ASXL1MT are associated with a loss of repressive histone methylation and increase in permissive histone methylation and acetylation in promoter regions. ASXL1MT are further associated with de novo accessibility of distal enhancers binding ETS transcription factors, targeting important leukemogenic driver genes. Chromatin remodeling of promoters and enhancers is strongly associated with gene expression and heterogenous among overexpressed genes. These results provide a comprehensive map of the transcriptome and chromatin landscape of ASXL1MT CMML, forming an important framework for the development of novel therapeutic strategies targeting oncogenic cis interactions.

Suggested Citation

  • Moritz Binder & Ryan M. Carr & Terra L. Lasho & Christy M. Finke & Abhishek A. Mangaonkar & Christopher L. Pin & Kurt R. Berger & Amelia Mazzone & Sandeep Potluri & Tamas Ordog & Keith D. Robertson & , 2022. "Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29142-6
    DOI: 10.1038/s41467-022-29142-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29142-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29142-6?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. Groemping, Ulrike, 2006. "Relative Importance for Linear Regression in R: The Package relaimpo," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 17(i01).
    2. Jane Merlevede & Nathalie Droin & Tingting Qin & Kristen Meldi & Kenichi Yoshida & Margot Morabito & Emilie Chautard & Didier Auboeuf & Pierre Fenaux & Thorsten Braun & Raphael Itzykson & Stéphane de , 2016. "Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    3. Antoine Campagne & Ming-Kang Lee & Dina Zielinski & Audrey Michaud & Stéphanie Corre & Florent Dingli & Hong Chen & Lara Z. Shahidian & Ivaylo Vassilev & Nicolas Servant & Damarys Loew & Eric Pasmant , 2019. "BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Johanna C. Scheuermann & Andrés Gaytán de Ayala Alonso & Katarzyna Oktaba & Nga Ly-Hartig & Robert K. McGinty & Sven Fraterman & Matthias Wilm & Tom W. Muir & Jürg Müller, 2010. "Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB," Nature, Nature, vol. 465(7295), pages 243-247, May.
    5. Shuhei Asada & Susumu Goyama & Daichi Inoue & Shiori Shikata & Reina Takeda & Tsuyoshi Fukushima & Taishi Yonezawa & Takeshi Fujino & Yasutaka Hayashi & Kimihito Cojin Kawabata & Tomofusa Fukuyama & Y, 2018. "Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    6. Anand Balasubramani & Antti Larjo & Jed A. Bassein & Xing Chang & Ryan B. Hastie & Susan M. Togher & Harri Lähdesmäki & Anjana Rao, 2015. "Cancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1–BAP1 complex," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    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. Nidhi Rohatgi & Wei Zou & Yongjia Li & Kevin Cho & Patrick L. Collins & Eric Tycksen & Gaurav Pandey & Carl J. DeSelm & Gary J. Patti & Anwesha Dey & Steven L. Teitelbaum, 2023. "BAP1 promotes osteoclast function by metabolic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yi Zhang & Guojia Xie & Ji-Eun Lee & Mohamad Zandian & Deepthi Sudarshan & Benjamin Estavoyer & Caroline Benz & Tiina Viita & Golareh Asgaritarghi & Catherine Lachance & Clémence Messmer & Leandro Sim, 2024. "ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Alam, M. Jahangir, 2020. "Capital misallocation: Cyclicality and sources," Journal of Economic Dynamics and Control, Elsevier, vol. 112(C).
    4. Neaimeh, Myriam & Salisbury, Shawn D. & Hill, Graeme A. & Blythe, Philip T. & Scoffield, Don R. & Francfort, James E., 2017. "Analysing the usage and evidencing the importance of fast chargers for the adoption of battery electric vehicles," Energy Policy, Elsevier, vol. 108(C), pages 474-486.
    5. Wang, Qinying & He, Hong S. & Liu, Kai & Zong, Shengwei & Du, Haibo, 2023. "Comparing simulated tree biomass from daily, monthly, and seasonal climate input of terrestrial ecosystem model," Ecological Modelling, Elsevier, vol. 483(C).
    6. Franck M. Ramaharo & Michael Fitiavana Randriamifidy, 2023. "Determinants of renewable energy consumption in Madagascar: Evidence from feature selection algorithms," Working Papers hal-04262240, HAL.
    7. Felipe Rosas-Díaz & David Gilberto García-Hernández & Cesar A. Juárez-Alvarado, 2024. "Development of Lignocellulosic-Based Insulation Materials from Agave fourcroydes and Washingtonia filifera for Use in Sustainable Buildings," Sustainability, MDPI, vol. 16(13), pages 1-17, June.
    8. Zhang, Yajun & Wang, Weilu & Li, Siyu & Zhu, Kuanyu & Hua, Xia & Harrison, Matthew Tom & Liu, Ke & Yang, Jianchang & Liu, Lijun & Chen, Yun, 2023. "Integrated management approaches enabling sustainable rice production under alternate wetting and drying irrigation," Agricultural Water Management, Elsevier, vol. 281(C).
    9. Su Jang & Yoo Seok Kang & Yoon Kyung Lee & Hee-Jong Koh, 2020. "Evaluating Multiple Allelic Combination to Determine Tiller Angle Variation in Rice," Agriculture, MDPI, vol. 10(10), pages 1-8, September.
    10. Hao Li & Tiantian Li & Wei-Yew Chang, 2023. "Family Identity, Place Identity, and Chinese Farmers’ Environment-Friendly Production Behavior," Agriculture, MDPI, vol. 13(7), pages 1-15, June.
    11. Dang, Yongcai & Qin, Lijie & Huang, Lirong & Wang, Jianqin & Li, Bo & He, Hongshi, 2022. "Water footprint of rain-fed maize in different growth stages and associated climatic driving forces in Northeast China," Agricultural Water Management, Elsevier, vol. 263(C).
    12. João Amador & Arne J. Nagengast, 2015. "The Effect of Bank Shocks on Firm-Level and Aggregate Investment," Working Papers w201515, Banco de Portugal, Economics and Research Department.
    13. Yayoi Natsume-Kitatani & Hiroshi Mamitsuka, 2016. "Classification of Promoters Based on the Combination of Core Promoter Elements Exhibits Different Histone Modification Patterns," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-18, March.
    14. Luong Hai Nguyen & Tsunemi Watanabe, 2017. "The Impact of Project Organizational Culture on the Performance of Construction Projects," Sustainability, MDPI, vol. 9(5), pages 1-21, May.
    15. Mitze, Timo & Reinkowski, Janina, 2010. "Testing the Validity of the Neoclassical Migration Model: Overall and Age-Group Specific Estimation Results for German Spatial Planning Regions," MPRA Paper 23616, University Library of Munich, Germany.
    16. Hüttner, Frank & Sunder, Marco, 2011. "Decomposing R2 with the Owen value," Working Papers 100, University of Leipzig, Faculty of Economics and Management Science.
    17. James Godwin & Mohan Govindasamy & Kiruba Nedounsejian & Eduardo March & Ronan Halton & Clara Bourbousse & Léa Wolff & Antoine Fort & Michal Krzyszton & Jesús López Corrales & Szymon Swiezewski & Fred, 2024. "The UBP5 histone H2A deubiquitinase counteracts PRCs-mediated repression to regulate Arabidopsis development," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    18. Cailin Wang & Enliang Guo & Yongfang Wang & Buren Jirigala & Yao Kang & Ye Zhang, 2023. "Spatiotemporal variations in drought and waterlogging and their effects on maize yields at different growth stages in Jilin Province, China," Natural Hazards: Journal of the International Society for the Prevention and Mitigation of Natural Hazards, Springer;International Society for the Prevention and Mitigation of Natural Hazards, vol. 118(1), pages 155-180, August.
    19. Yangyi Zhou & Jiangping Wang, 2023. "The Composition and Assembly of Soil Microbial Communities Differ across Vegetation Cover Types of Urban Green Spaces," Sustainability, MDPI, vol. 15(17), pages 1-15, August.
    20. Yige Wu & Nadezhda V. Terekhanova & Wagma Caravan & Nataly Naser Al Deen & Preet Lal & Siqi Chen & Chia-Kuei Mo & Song Cao & Yize Li & Alla Karpova & Ruiyang Liu & Yanyan Zhao & Andrew Shinkle & Ilya , 2023. "Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-25, 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_s41467-022-29142-6. 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.