ArticleNature communications2020
A distal regulatory region of a class I human histone deacetylase.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
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- Unraveling the role of HDAC3 as an immunotherapy prognostic biomarker and therapeutic target in advanced non-small cell lung cancer.Respiratory research · 2025Article
- Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051.Communications biology · 2025Article
- Solution-state methyl NMR spectroscopy of large non-deuterated proteins enabled by deep neural networks.Nature communications · 2024Article
- Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors.Journal of medicinal chemistry · 2024Article
- Picornavirus 3C Proteins Intervene in Host Cell Processes through Proteolysis and Interactions with RNA.Viruses · 2023Review
- Intrinsic structural dynamics dictate enzymatic activity and inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.Nature communications · 2023Article
- Carbon quantum dots in bioimaging and biomedicines.Frontiers in bioengineering and biotechnology · 2023Review
- Methionine 274 Is Not the Determining Factor for Selective Inhibition of Histone Deacetylase 8 (HDAC8) by L-Shaped Inhibitors.International journal of molecular sciences · 2022Article
- IGF-dependent dynamic modulation of a protease cleavage site in the intrinsically disordered linker domain of human IGFBP2.Proteins · 2022Article
- The role of structural dynamics in the thermal adaptation of hyperthermophilic enzymes.Frontiers in molecular biosciences · 2022Article
- Aromatic side-chain flips orchestrate the conformational sampling of functional loops in human histone deacetylase 8.Chemical science · 2021Article
- FID-Net: A versatile deep neural network architecture for NMR spectral reconstruction and virtual decoupling.Journal of biomolecular NMR · 2021Article
- Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders.Journal of structural biology · 2021Article
- Characterization of Histone Deacetylase Mechanisms in Cancer Development.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Histone deacetylases (HDACs) are key enzymes in epigenetics and important drug targets in cancer biology. Whilst it has been established that HDACs regulate many cellular processes, far less is known about the regulation of these enzymes themselves. Here, we show that HDAC8 is allosterically regulated by shifts in populations between exchanging states. An inactive state is identified, which is stabilised by a range of mutations and resembles a sparsely-populated state in equilibrium with active HDAC8. Computational models show that the inactive and active states differ by small changes in a regulatory region that extends up to 28 Å from the active site. The regulatory allosteric region identified here in HDAC8 corresponds to regions in other class I HDACs known to bind regulators, thus suggesting a general mechanism. The presented results pave the way for the development of allosteric HDAC inhibitors and regulators to improve the therapy for several disease states.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.