IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41793-7.html
   My bibliography  Save this article

Acetylation reprograms MITF target selectivity and residence time

Author

Listed:
  • Pakavarin Louphrasitthiphol

    (University of Oxford, Headington
    University of Tsukuba)

  • Alessia Loffreda

    (Ospedale San Raffaele)

  • Vivian Pogenberg

    (European Molecular Biology Laboratory, Hamburg Unit
    University Hamburg Medical Centre Hamburg-Eppendorf)

  • Sarah Picaud

    (University of Oxford, Headington)

  • Alexander Schepsky

    (University of Oxford, Headington
    University of Iceland)

  • Hans Friedrichsen

    (University of Oxford, Headington)

  • Zhiqiang Zeng

    (MRC Human Genetics Unit & Edinburgh Cancer Research Centre)

  • Anahita Lashgari

    (CHU de Québec – Université Laval Research Center)

  • Benjamin Thomas

    (University of Oxford)

  • E. Elizabeth Patton

    (MRC Human Genetics Unit & Edinburgh Cancer Research Centre)

  • Matthias Wilmanns

    (European Molecular Biology Laboratory, Hamburg Unit
    University Hamburg Medical Centre Hamburg-Eppendorf)

  • Panagis Filippakopoulos

    (University of Oxford, Headington)

  • Jean-Philippe Lambert

    (CHU de Québec – Université Laval Research Center)

  • Eiríkur Steingrímsson

    (University of Iceland)

  • Davide Mazza

    (Ospedale San Raffaele
    Università Vita-Salulte San Raffaele)

  • Colin R. Goding

    (University of Oxford, Headington)

Abstract

The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.

Suggested Citation

  • Pakavarin Louphrasitthiphol & Alessia Loffreda & Vivian Pogenberg & Sarah Picaud & Alexander Schepsky & Hans Friedrichsen & Zhiqiang Zeng & Anahita Lashgari & Benjamin Thomas & E. Elizabeth Patton & M, 2023. "Acetylation reprograms MITF target selectivity and residence time," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41793-7
    DOI: 10.1038/s41467-023-41793-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41793-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41793-7?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. Fangjie Zhu & Lucas Farnung & Eevi Kaasinen & Biswajyoti Sahu & Yimeng Yin & Bei Wei & Svetlana O. Dodonova & Kazuhiro R. Nitta & Ekaterina Morgunova & Minna Taipale & Patrick Cramer & Jussi Taipale, 2018. "The interaction landscape between transcription factors and the nucleosome," Nature, Nature, vol. 562(7725), pages 76-81, October.
    2. Levi A. Garraway & Hans R. Widlund & Mark A. Rubin & Gad Getz & Aaron J. Berger & Sridhar Ramaswamy & Rameen Beroukhim & Danny A. Milner & Scott R. Granter & Jinyan Du & Charles Lee & Stephan N. Wagne, 2005. "Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma," Nature, Nature, vol. 436(7047), pages 117-122, July.
    3. Timothy J. Hemesath & E. Roydon Price & Clifford Takemoto & Tina Badalian & David E. Fisher, 1998. "MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes," Nature, Nature, vol. 391(6664), pages 298-301, January.
    4. Judith Müller & Oscar Krijgsman & Jennifer Tsoi & Lidia Robert & Willy Hugo & Chunying Song & Xiangju Kong & Patricia A. Possik & Paulien D. M. Cornelissen-Steijger & Marnix H Geukes Foppen & Kristel , 2014. "Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    5. Colin R. Lickwar & Florian Mueller & Sean E. Hanlon & James G. McNally & Jason D. Lieb, 2012. "Genome-wide protein–DNA binding dynamics suggest a molecular clutch for transcription factor function," Nature, Nature, vol. 484(7393), pages 251-255, April.
    6. Alessia Loffreda & Emanuela Jacchetti & Sofia Antunes & Paolo Rainone & Tiziana Daniele & Tatsuya Morisaki & Marco E. Bianchi & Carlo Tacchetti & Davide Mazza, 2017. "Live-cell p53 single-molecule binding is modulated by C-terminal acetylation and correlates with transcriptional activity," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    7. Suzanne Carreira & Jane Goodall & Isil Aksan & S. Anna La Rocca & Marie-Dominique Galibert & Laurence Denat & Lionel Larue & Colin R. Goding, 2005. "Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression," Nature, Nature, vol. 433(7027), pages 764-769, February.
    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. Amir Shahein & Maria López-Malo & Ivan Istomin & Evan J. Olson & Shiyu Cheng & Sebastian J. Maerkl, 2022. "Systematic analysis of low-affinity transcription factor binding site clusters in vitro and in vivo establishes their functional relevance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Miles C. Andrews & Junna Oba & Chang-Jiun Wu & Haifeng Zhu & Tatiana Karpinets & Caitlin A. Creasy & Marie-Andrée Forget & Xiaoxing Yu & Xingzhi Song & Xizeng Mao & A. Gordon Robertson & Gabriele Roma, 2022. "Multi-modal molecular programs regulate melanoma cell state," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    4. Zing Tsung-Yeh Tsai & Shin-Han Shiu & Huai-Kuang Tsai, 2015. "Contribution of Sequence Motif, Chromatin State, and DNA Structure Features to Predictive Models of Transcription Factor Binding in Yeast," PLOS Computational Biology, Public Library of Science, vol. 11(8), pages 1-22, August.
    5. Michaël Noë & Dimitrios Mathios & Akshaya V. Annapragada & Shashikant Koul & Zacharia H. Foda & Jamie E. Medina & Stephen Cristiano & Christopher Cherry & Daniel C. Bruhm & Noushin Niknafs & Vilmos Ad, 2024. "DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Barry R Zeeberg & William Reinhold & René Snajder & Gerhard G Thallinger & John N Weinstein & Kurt W Kohn & Yves Pommier, 2012. "Functional Categories Associated with Clusters of Genes That Are Co-Expressed across the NCI-60 Cancer Cell Lines," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-10, January.
    7. Tianbao Li & Qi Liu & Zhong Chen & Kun Fang & Furong Huang & Xueqi Fu & Qianben Wang & Victor X. Jin, 2022. "Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Chuanyuan Wei & Wei Sun & Kangjie Shen & Jingqin Zhong & Wanlin Liu & Zixu Gao & Yu Xu & Lu Wang & Tu Hu & Ming Ren & Yinlam Li & Yu Zhu & Shaoluan Zheng & Ming Zhu & Rongkui Luo & Yanwen Yang & Yingy, 2023. "Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Anastasia Samarkina & Markus Kirolos Youssef & Paola Ostano & Soumitra Ghosh & Min Ma & Beatrice Tassone & Tatiana Proust & Giovanna Chiorino & Mitchell P. Levesque & Sandro Goruppi & Gian Paolo Dotto, 2023. "Androgen receptor is a determinant of melanoma targeted drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Matteo Mazzocca & Alessia Loffreda & Emanuele Colombo & Tom Fillot & Daniela Gnani & Paola Falletta & Emanuele Monteleone & Serena Capozi & Edouard Bertrand & Gaelle Legube & Zeno Lavagnino & Carlo Ta, 2023. "Chromatin organization drives the search mechanism of nuclear factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Claudia Capparelli & Timothy J. Purwin & McKenna Glasheen & Signe Caksa & Manoela Tiago & Nicole Wilski & Danielle Pomante & Sheera Rosenbaum & Mai Q. Nguyen & Weijia Cai & Janusz Franco-Barraza & Ric, 2022. "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Luopin Wang & Aryamav Pattnaik & Subhransu Sekhar Sahoo & Ella G. Stone & Yuxin Zhuang & Annaleigh Benton & Md Tajmul & Srishti Chakravorty & Deepika Dhawan & My An Nguyen & Isabella Sirit & Kyle Mund, 2024. "Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Michael F. Emmons & Richard L. Bennett & Alberto Riva & Kanchan Gupta & Larissa Anastasio Da Costa Carvalho & Chao Zhang & Robert Macaulay & Daphne Dupéré-Richér & Bin Fang & Edward Seto & John M. Koo, 2023. "HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Anushweta Asthana & Parameshwaran Ramanan & Alexander Hirschi & Keelan Z. Guiley & Tilini U. Wijeratne & Robert Shelansky & Michael J. Doody & Haritha Narasimhan & Hinrich Boeger & Sarvind Tripathi & , 2022. "The MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Marios G. Koliopoulos & Reyhan Muhammad & Theodoros I. Roumeliotis & Fabienne Beuron & Jyoti S. Choudhary & Claudio Alfieri, 2022. "Structure of a nucleosome-bound MuvB transcription factor complex reveals DNA remodelling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Marta Losa & Iros Barozzi & Marco Osterwalder & Viviana Hermosilla-Aguayo & Angela Morabito & Brandon H. Chacón & Peyman Zarrineh & Ausra Girdziusaite & Jean Denis Benazet & Jianjian Zhu & Susan Macke, 2023. "A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    18. Vivekanandan Ramalingam & Xinyang Yu & Brian D. Slaughter & Jay R. Unruh & Kaelan J. Brennan & Anastasiia Onyshchenko & Jeffrey J. Lange & Malini Natarajan & Michael Buck & Julia Zeitlinger, 2023. "Lola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Anna Berenson & Ryan Lane & Luis F. Soto-Ugaldi & Mahir Patel & Cosmin Ciausu & Zhaorong Li & Yilin Chen & Sakshi Shah & Clarissa Santoso & Xing Liu & Kerstin Spirohn & Tong Hao & David E. Hill & Marc, 2023. "Paired yeast one-hybrid assays to detect DNA-binding cooperativity and antagonism across transcription factors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Pengcheng Zhang & Haochen Wang & Hanwen Xu & Lei Wei & Liyang Liu & Zhirui Hu & Xiaowo Wang, 2023. "Deep flanking sequence engineering for efficient promoter design using DeepSEED," Nature Communications, Nature, vol. 14(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:14:y:2023:i:1:d:10.1038_s41467-023-41793-7. 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.