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

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Turnbull, Robert E., Fairall, Louise, Saleh, Almutasem, Kelsall, Emma, Morris, Kyle L., Ragan, T. J., Savva, Christos G., Chandru, Aditya, Millard, Christopher J., Makarova, Olga V., Smith, Corinne J., Roseman, Alan M., Fry, Andrew M., Cowley, Shaun M. and Schwabe, John W. R. (2020) The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure. Nature Communications, 11 (1). 3252. doi:10.1038/s41467-020-17078-8

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Official URL: http://dx.doi.org/10.1038/s41467-020-17078-8

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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.

Item Type: Journal Article
Subjects: Q Science > QA Mathematics
Q Science > QH Natural history
Q Science > QL Zoology
Q Science > QP Physiology
Divisions: Faculty of Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Histones, Histone deacetylase, Embryology, Genomes
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 26 June 2020
Dates:
DateEvent
26 June 2020Published
5 June 2020Accepted
Volume: 11
Number: 1
Article Number: 3252
DOI: 10.1038/s41467-020-17078-8
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
055663/Z/98/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
MC_PC_17136[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
WT100237/Z/12/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
BB/N002954/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MR/J009202/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265

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