IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17078-8.html
   My bibliography  Save this article

The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure

Author

Listed:
  • Robert E. Turnbull

    (University of Leicester
    University of Leicester)

  • Louise Fairall

    (University of Leicester
    University of Leicester)

  • Almutasem Saleh

    (University of Leicester
    University of Leicester
    Institute of Clinical Sciences, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus)

  • Emma Kelsall

    (University of Leicester
    AstraZeneca, Milstein Building, Granta Park)

  • Kyle L. Morris

    (University of Warwick
    MRC London Institute of Medical Sciences, Hammersmith Hospital Campus)

  • T. J. Ragan

    (University of Leicester)

  • Christos G. Savva

    (University of Leicester)

  • Aditya Chandru

    (University of Leicester
    University of Cambridge)

  • Christopher J. Millard

    (University of Leicester
    University of Leicester)

  • Olga V. Makarova

    (University of Leicester)

  • Corinne J. Smith

    (University of Warwick)

  • Alan M. Roseman

    (University of Manchester)

  • Andrew M. Fry

    (University of Leicester)

  • Shaun M. Cowley

    (University of Leicester)

  • John W. R. Schwabe

    (University of Leicester
    University of Leicester)

Abstract

MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Mice lacking the MiDAC proteins, DNTTIP1 or MIDEAS, die with identical phenotypes during late embryogenesis due to perturbations in gene expression that result in heart malformation and haematopoietic failure. This suggests that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes. Consistent with this, the cryoEM structure of MiDAC reveals a unique and distinctive mode of assembly. Four copies of HDAC1 are positioned at the periphery with outward-facing active sites suggesting that the complex may target multiple nucleosomes implying a processive deacetylase function.

Suggested Citation

  • Robert E. Turnbull & Louise Fairall & Almutasem Saleh & Emma Kelsall & Kyle L. Morris & T. J. Ragan & Christos G. Savva & Aditya Chandru & Christopher J. Millard & Olga V. Makarova & Corinne J. Smith , 2020. "The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17078-8
    DOI: 10.1038/s41467-020-17078-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17078-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17078-8?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mandy S. M. Wan & Reyhan Muhammad & Marios G. Koliopoulos & Theodoros I. Roumeliotis & Jyoti S. Choudhary & Claudio Alfieri, 2023. "Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Jonathan W. Markert & Seychelle M. Vos & Lucas Farnung, 2023. "Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex," Nature Communications, Nature, vol. 14(1), pages 1-11, 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:11:y:2020:i:1:d:10.1038_s41467-020-17078-8. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.