Erasers of Histone Acetylation: The Histone Deacetylase Enzymes

Seto, Edward; Yoshida, Minoru

doi:10.1101/cshperspect.a018713

Cited by 1,380 publications

(1,097 citation statements)

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“…During the same time, Sternglanz and coworkers (Kleff et al 1995) and Gottschling and coworkers (Parthun et al 1996) also identified a histone acetyltransferase called HAT1 that was initially proposed to be a cytoplasmic specific acetyltransferase and later shown to also harbor nuclear functions (Ruiz-Garcia et al 1998;Ai and Parthun 2004;Poveda et al 2004). In the same year, Schreiber and colleagues isolated a mammalian histone deacetylase (HDAC) that was highly homologous to a previously characterized transcriptional repressor Rpd3 (covered in Seto and Yoshida 2014), also with conservation from yeast to man (Taunton et al 1996). Subsequent to these groundbreaking studies, other HATs and HDACs were identified along with other types of enzymes that modify histones Marmorstein and Trievel 2009).…”

Section: Introduction To Writers Erasers and Readers Of Histonesmentioning

confidence: 99%

“…This article will cover what is known to date about the structure, mechanism of action, and inhibition of HAT enzymes. Readers are directed to the collection's article on HDACs dealing with the topic of histone lysine deacetylation (Seto and Yoshida 2014, and other excellent review articles therein).…”

Section: Introduction To Writers Erasers and Readers Of Histonesmentioning

confidence: 99%

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Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition

Marmorstein

Zhou

2014

Cold Spring Harbor Perspectives in Biology

442

327

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SUMMARYHistone acetylation marks are written by histone acetyltransferases (HATs) and read by bromodomains (BrDs), and less commonly by other protein modules. These proteins regulate many transcription-mediated biological processes, and their aberrant activities are correlated with several human diseases. Consequently, small molecule HAT and BrD inhibitors with therapeutic potential have been developed. Structural and biochemical studies of HATs and BrDs have revealed that HATs fall into distinct subfamilies containing a structurally related core for cofactor binding, but divergent flanking regions for substratespecific binding, catalysis, and autoregulation. BrDs adopt a conserved left-handed four-helix bundle to recognize acetyllysine; divergent loop residues contribute to substrate-specific acetyllysine recognition.

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Section: Introduction To Writers Erasers and Readers Of Histonesmentioning

confidence: 99%

Section: Introduction To Writers Erasers and Readers Of Histonesmentioning

confidence: 99%

Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition

Marmorstein

Zhou

2014

Cold Spring Harbor Perspectives in Biology

442

327

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“…The Reduced Potassium Deficiency3 (RPD3)-like family and Silent Information Regulator2 (SIR2)-like (sirtuin) family are zinc dependent and NAD (+) dependent, respectively. The RPD3-like family is divided into three classes (I, II, and IV), based on their homology to yeast HDACs (Bolden et al, 2006;Seto and Yoshida, 2014;Verdin and Ott, 2015). Plants also have evolved a plant-specific HDAC (HD-tuin) family (Brosch et al, 1996;Lusser et al, 1997;Hollender and Liu, 2008).…”

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confidence: 99%

The Distinct Roles of Class I and II RPD3-Like Histone Deacetylases in Salinity Stress Response

et al. 2017

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ORCID IDs: 0000-0002-7750-6056 (M.U.); 0000-0002-3979-3947 (A.M.); 0000-0001-8288-0467 (M.S.).Histone acetylation is an essential process in the epigenetic regulation of diverse biological processes, including environmental stress responses in plants. Previously, our research group identified a histone deacetylase (HDAC) inhibitor (HDI) that confers salt tolerance in Arabidopsis (Arabidopsis thaliana). In this study, we demonstrate that class I HDAC (HDA19) and class II HDACs (HDA5/14/15/18) control responses to salt stress through different pathways. The screening of 12 different selective HDIs indicated that seven newly reported HDIs enhance salt tolerance. Genetic analysis, based on a pharmacological study, identified which HDACs function in salinity stress tolerance. In the wild-type Columbia-0 background, hda19 plants exhibit tolerance to high-salinity stress, while hda5/14/15/18 plants exhibit hypersensitivity to salt stress. Transcriptome analysis revealed that the effect of HDA19 deficiency on the response to salinity stress is distinct from that of HDA5/14/15/18 deficiencies. In hda19 plants, the expression levels of stress tolerance-related genes, late embryogenesis abundant proteins that prevent protein aggregation and positive regulators such as ABI5 and NAC019 in abscisic acid signaling, were induced strongly relative to the wild type. Neither of these elements was up-regulated in the hda5/14/15/18 plants. The mutagenesis of HDA19 by genome editing in the hda5/14/15/18 plants enhanced salt tolerance, suggesting that suppression of HDA19 masks the phenotype caused by the suppression of class II HDACs in the salinity stress response. Collectively, our results demonstrate that HDIs that inhibit class I HDACs allow the rescue of plants from salinity stress regardless of their selectivity, and they provide insight into the hierarchal regulation of environmental stress responses through HDAC isoforms.Histones are DNA-packaging proteins that provide stability to the genome by preventing physical genotoxicity (e.g. DNA breaks; Luger et al., 1997;Downs et al., 2007). They also have been considered to originally function as regulators of mRNA expression before the divergence of the Archaea and Eukarya (Ammar et al., 2012). A variety of chemical modifications (acetylation, methylation, phosphorylation, etc.) to the N tails of histones are one of the properties that enable the regulation of mRNA expression, which is generally conserved in eukaryotes (Jenuwein and Allis, 2001;Kouzarides, 2007). Chromatin possesses a diverse array of chemical moieties that allows it to contain and transmit information that is independent of the genetic code (i.e. epigenetic) and regulate gene expression levels. Epigenetic regulation is considered to be profoundly associated with plant development and adaptation to the environment. A complete understanding of the coordinated regulation of gene expression by histone modifications, however, is still lacking in plants. The role of epigenetic regulation in the abiotic stress response...

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“…HDAC6 belongs to class IIb HDACs. Its structure is quite unique among all HDACs, in that it contains two functional deacetylase domains in tandem and a zinc finger domain in the C-terminus (2,3). HDAC6 participates in numerous biological and pathologic processes, such as cell migration, DNA damage response and oncogenesis, through modulating its substrates (4)(5)(6)(7).…”

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confidence: 99%

Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity

Xiang

Zhang

et al. 2018

Journal of Biological Chemistry

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Histone deacetylase 6 (HDAC6), a class IIb HDAC, plays an important role in many biological and pathological processes. Previously, we found that ERK1, a downstream kinase in the MAPK signaling pathway, phosphorylates HDAC6, thereby increasing HDAC6-mediated deacetylation of α-tubulin. However, whether HDAC6 reciprocally modulates ERK1 activity is unknown. Here, we report that both ERK1 and 2 are acetylated and that HDAC6 promotes ERK1 activity via deacetylation. Briefly, we found that both ERK1 and 2 physically interact with HDAC6. Endogenous ERK1/2 acetylation levels increased upon treatment with a pan-HDAC inhibitor, an HDAC6-specific inhibitor or depletion of HDAC6, suggesting that HDAC6 deacetylates ERK1/2. We also noted that the acetyltransferases CBP and p300 both can acetylate ERK1/2. Acetylated ERK1 exhibits reduced enzymatic activity toward the transcription factor ELK1, a well-known ERK1 substrate. Furthermore, mass spectrometry analysis indicated Lys-72 as an acetylation site in the ERK1 N-terminus, adjacent to Lys-71, which binds to ATP, suggesting that acetylation status of Lys-72 may affect ERK1 ATP binding. Interestingly, an acetylation-mimicking ERK1 mutant (K72Q) exhibited less phosphorylation than the WT enzyme and a deacetylationmimicking mutant (K72R). Of note, the K72Q mutant displayed decreased enzymatic activity in an in vitro kinase assay and in a cellular luciferase assay compared with the WT and K72R mutant. Taken together, our findings suggest that HDAC6 stimulates ERK1 activity. Along with our previous report that ERK1 promotes HDAC6 activity, we propose that HDAC6 and ERK1 may form a positive feedforward loop, which might play a role in cancer.Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are the enzymes that regulate core histones and non-histone proteins by deacetylation and acetylation, respectively (1). HATs acetylate proteins via adding acetyl groups to lysine residues, while HDACs catalyze a reverse reaction by removing the acetyl group from lysine residues. Up to now, a total of 18 HDACs are identified in humans and grouped HDAC6 deacetylates ERK12 into four classes based on their sequence similarity to yeast orthologs (2). Class I HDACs are homologous to yeast reduced potassium dependency 3 (Rpd3) and include HDACs 1, 2, 3 and 8. Class II HDACs are homologous to yeast histone deacetylase 1 (HdaI) and are further divided into class IIa and class IIb. Class IIa contains HDACs 4, 5, 7 and 9, and class IIb includes HDACs 6 and 10. HDAC11 is the only member in class IV. The deacetylase activity of HDAC classes I, II and IV is zinc-dependent. Class III HDACs, also knowns as sirtuins, are homologous to yeast silent information regulator 2 (Sir2), and the deacetylase activity of this class is oxidized nicotinamide adenine dinucleotide (NAD + )-dependent. HDAC6 belongs to class IIb HDACs. Its structure is quite unique among all HDACs, in that it contains two functional deacetylase domains in tandem and a zinc finger domain in the C-terminus (2,3). HDAC6...

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Erasers of Histone Acetylation: The Histone Deacetylase Enzymes

Cited by 1,380 publications

References 120 publications

Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition

Writers and Readers of Histone Acetylation: Structure, Mechanism, and Inhibition

The Distinct Roles of Class I and II RPD3-Like Histone Deacetylases in Salinity Stress Response

Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity

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