The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure
Year: 2020
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Awards: 200kV field emission gun cryo-electron microscope system., The Molecular Functioning of HDAC:co-repressor complexes., A facility for 3D cellular imaging that bridges light and electron microscopy, G4072162133, The Molecular Functioning of HDAC:co-repressor complexes., G479450953, G4802663688, A Midlands Regional Cryo-EM facility, Understanding the contribution of inositol phosphate signalling to class-1 HDAC complex function, G8482136486, Understanding the essential requirement for HDAC1 and HDAC2 in tissue development and homeostasis: implications for disease and therapy.
OpenAlex ID: W3037025246