Histone acetylation and deacetylation in yeast

Kurdistani, Siavash K.; Grunstein, Michael

doi:10.1038/nrm1075

Cited by 608 publications

(476 citation statements)

References 91 publications

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“…Acetylation, in general, correlates with the establishment of an open chromatin conformation that is transcriptionally active (Kurdistani and Grunstein, 2003;Vaquero et al, 2003). This is in contrast to the case of hypoacetylation of the H3 and H4 tails that correlates with a compacted chromatin structure refractory to transcription (Kurdistani and Grunstein, 2003;Calestagne-Morelli and Ausio´, 2006). The covalent addition of an acetyl group to the e-amino group of a lysine residue has been postulated to affect chromatin at two levels.…”

Section: Acetylation Of Histonesmentioning

confidence: 99%

“…Acetylation is a reversible modification with a rapid turnover due to the highly dynamic equilibrium between two different groups of enzymes, HATs (Histone Acetyl Transferases) and Histone Deacetylases (HDACs). The balance between these two activities is key to generating the appropriate changes in chromatin as part of the cellular response to environmental changes (Kurdistani and Grunstein, 2003;Vaquero et al, 2003).…”

Section: Acetylation Of Histonesmentioning

confidence: 99%

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NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

2007

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Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation of chromatin structure. Accumulating data suggest that these deacetylases acquired new roles as genomic complexity increased, including deacetylation of non-histone proteins and functional diversification in mammals. However, the intrinsic regulation of chromatin structure in species as diverse as yeast and humans, underscores the pressure to conserve core functions of class III HDACs, which are also known as Sirtuins. One of the key factors that might have contributed to this preservation is the intimate relationship between some members of this group of proteins (SirT1, SirT2 and SirT3) and deacetylation of a specific residue in histone H4, lysine 16 (H4K16). Evidence accumulated over the years has uncovered a unique role for H4K16 in chromatin structure throughout eukaryotes. Here, we review the recent findings about the functional relationship between H4K16 and the Sir2 class of deacetylases and how that relationship might impact aging and diseases including cancer and diabetes.

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Section: Acetylation Of Histonesmentioning

confidence: 99%

Section: Acetylation Of Histonesmentioning

confidence: 99%

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

2007

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“…Although the role of chromatin modifications in replication is still poorly understood, recent studies provide evidence that post-translational chromatin modifications can control the efficiency and/or timing of replication origin activity (Vogelauer et al, 2002;Zhang et al, 2002;Kurdistani and Grunstein, 2003;Lin et al, 2003;Perry et al, 2004;Azuara et al, 2006). In yeast, histone acetylation in the vicinity of replication origin is an important determinant of replication timing and it appears that higher level of histone acetylation coincides with earlier firing of an origin (Vogelauer et al, 2002).…”

Section: Replicationmentioning

confidence: 99%

“…We also discuss the implications from the recent findings regarding the process of tumorigenesis. Readers are also directed to several excellent reviews on different aspects of histone acetylation and HATs Kouzarides, 2000;Cheung et al, 2000a, b;Carrozza et al, 2003;Kurdistani and Grunstein, 2003;Yang, 2004;Squatrito et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Orchestration of chromatin-based processes: mind the TRRAP

et al. 2007

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Chromatin modifications at core histones including acetylation, methylation, phosphorylation and ubiquitination play an important role in diverse biological processes. Acetylation of specific lysine residues within the N terminus tails of core histones is arguably the most studied histone modification; however, its precise roles in different cellular processes and how it is disrupted in human diseases remain poorly understood. In the last decade, a number of histone acetyltransferases (HATs) enzymes responsible for histone acetylation, has been identified and functional studies have begun to unravel their biological functions. The activity of many HATs is dependent on HAT complexes, the multiprotein assemblies that contain one HAT catalytic subunit, adapter proteins, several other molecules of unknown function and a large protein called TRansformation/tRanscription domain-Associated Protein (TRRAP). As a common component of many HAT complexes, TRRAP appears to be responsible for the recruitment of these complexes to chromatin during transcription, replication and DNA repair. Recent studies have shed new light on the role of TRRAP in HAT complexes as well as mechanisms by which it mediates diverse cellular processes. Thus, TRRAP appears to be responsible for a concerted and context-dependent recruitment of HATs and coordination of distinct chromatin-based processes, suggesting that its deregulation may contribute to diseases. In this review, we summarize recent developments in our understanding of the function of TRRAP and TRRAP-containing HAT complexes in normal cellular processes and speculate on the mechanism underlying abnormal events that may lead to human diseases such as cancer.

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“…A shift in the balance of acetylation on chromatin may result in changes in the regulation of patterns of gene expression. [1][2][3][4] Since many cancers are associated with aberrant transcriptional activity, and the HDACs can affect transcription factors and gene regulation, these enzymes have been identified as attractive targets for cancer therapy. Indeed, chemical inhibitors of HDACs have been shown to inhibit tumor cell growth and induce differentiation and cell death.…”

Section: Introductionmentioning

confidence: 99%

Chemistry, Biology, and QSAR Studies of Substituted Biaryl Hydroxamates and Mercaptoacetamides as HDAC Inhibitors—Nanomolar‐Potency Inhibitors of Pancreatic Cancer Cell Growth

et al. 2008

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The histone deacetylases (HDACs) are able to regulate gene expression and inhibitors of the HDACs (HDACIs) hold promise in the treatment of cancer as well as a variety of neurodegenerative diseases. To investigate the possibility to achieve some measure of isoform selectivity in the inhibition of the HDACs, we prepared a small series of 2,4′-diaminobiphenyl ligands functionalized at the para-amino group with an appendage containing either a hydroxamate or a mercaptoacetamide group and coupled to an amino acid residue at the ortho-amino group. A smaller series of substituted phenylthiazoles was also explored. Some of these newly synthesized ligands show low nM potency in the HDAC inhibition assays and display micromolar to low nanomolar IC 50 values when tested against five pancreatic cancer cell lines. The isoform selectivity of these ligands for the Class I HDACs (HDAC1-3 and 8) and Class IIb HDACs (HDAC6 and HDAC10) together with QSAR studies of their correlation with the lipophilicity are presented. Of particular interest is the HDAC6 selectivity of the mercaptoacetamides.

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Histone acetylation and deacetylation in yeast

Cited by 608 publications

References 91 publications

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

Orchestration of chromatin-based processes: mind the TRRAP

Chemistry, Biology, and QSAR Studies of Substituted Biaryl Hydroxamates and Mercaptoacetamides as HDAC Inhibitors—Nanomolar‐Potency Inhibitors of Pancreatic Cancer Cell Growth

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