The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure.
Amino Acid Sequence
Animals
Cell Line
Chromatin
/ metabolism
Chromosomes, Mammalian
/ metabolism
Embryo, Mammalian
/ cytology
Embryonic Development
Fibroblasts
/ metabolism
Gene Regulatory Networks
Heterozygote
Histone Deacetylases
/ metabolism
Homozygote
Humans
Mice, Inbred C57BL
Mice, Knockout
Mitosis
Models, Molecular
Multiprotein Complexes
/ chemistry
Nuclear Proteins
/ metabolism
Protein Domains
Protein Multimerization
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 06 2020
26 06 2020
Historique:
received:
21
01
2020
accepted:
05
06
2020
entrez:
28
6
2020
pubmed:
28
6
2020
medline:
1
9
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32591534
doi: 10.1038/s41467-020-17078-8
pii: 10.1038/s41467-020-17078-8
pmc: PMC7319964
doi:
Substances chimiques
Chromatin
0
Multiprotein Complexes
0
Nuclear Proteins
0
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3252Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N002954/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J009202/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100237/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_17136
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 055663/Z/98/Z
Pays : United Kingdom
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