Phosphorylation of Serine 10 in Histone H3 Is Functionally Linked In Vitro and In Vivo to Gcn5-Mediated Acetylation at Lysine 14

Lo, Wan Sheng; Trievel, Raymond C.; Rojas, Jeannie R.; Duggan, Laura J.; Hsu, Jer Yuan; Allis, C. David; Marmorstein, Ronen; Berger, Shelley L.

doi:10.1016/s1097-2765(00)80257-9

Cited by 515 publications

(405 citation statements)

References 59 publications

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“…In some cases, pairs of enzymes with distinct activities may function sequentially to potentiate function. Such is the case for the Snf1 histone kinase and the HAT Gcn5p (Lo et al, 2000(Lo et al, , 2001. In other cases, two HATs with different substrate specificities may act on the same gene to establish a characteristic pattern of modification, as has been observed for Gcn5p and Esa1p (Vogelauer et al, 2000).…”

Section: Hats and Hdacs Are Both Required For Functional Optimizationmentioning

confidence: 83%

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Clarke

Samal

Pillus

2006

MBoC

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Among acetyltransferases, the MYST family enzyme Esa1p is distinguished for its essential function and contribution to transcriptional activation and DNA double-stranded break repair. Here we report that Esa1p also plays a key role in silencing RNA polymerase II (Pol II)-transcribed genes at telomeres and within the ribosomal DNA (rDNA) of the nucleolus. These effects are mediated through Esa1p's HAT activity and correlate with changes within the nucleolus. Esa1p is enriched within the rDNA, as is the NAD-dependent protein deacetylase Sir2p, and the acetylation levels of key Esa1p histone targets are reduced in the rDNA in esa1 mutants. Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA recombination, esa1 effects are more modest yet result in distinct structural changes of rDNA chromatin. Surprisingly, increased expression of ESA1 can bypass the requirement for Sir2p in rDNA silencing, suggesting that these two enzymes with seemingly opposing activities both contribute to achieve optimal nucleolar chromatin structure and function. INTRODUCTIONHistone modifications such as phosphorylation, methylation, acetylation, and deacetylation provide a mechanism by which chromatin structure is modulated to affect gene expression both positively and negatively (for reviews see Strahl and Allis, 2000;Iizuka and Smith, 2003;Kurdistani and Grunstein, 2003). The acetylation of lysine residues on histone N-terminal tails is classically linked to increases in gene expression and more directly to roles in transcriptional activation. By contrast, deacetylation of histones is most frequently correlated with transcriptionally silent chromatin. As more is learned about the enzymes catalyzing these modifications, the histone acetyltransferases (HATs) and histone deacetylases (HDACs), simple functional distinctions between acetylation and deacetylation of histones do not hold (Iizuka and Smith, 2003). For example, in several organisms, mutations in RPD3, a gene encoding a deacetylase, lead to increases in silencing rather than the expected decreases (DeRubertis et al., 1996;Rundlett et al., 1996). This brings forward the possibility that histone acetylation may play an important part in both silent and active chromatin. In addition, coactivator proteins, such as the histone acetyltransferases p300 and CBP and nuclear hormone receptors, appear to have roles in transcriptional repression through acetylation and association with particular binding partners (for examples, see Chen and Li, 1998;Waltzer and Bienz, 1998;Baluchamy et al., 2003;Girdwood et al., 2003;Rajabi et al., 2005). Thus, understanding of multiple roles for acetylation in controlling gene expression is expanding.In Saccharomyces cerevisiae, there are three regions of the genome controlled by chromatin-mediated transcriptional silencing: telomeres, the silent mating-type loci HMR and HML, and the rDNA array. Many factors are important for transcriptional silencing at subsets of these loci including the four core histones, the repressor activator protein Rap1...

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Section: Hats and Hdacs Are Both Required For Functional Optimizationmentioning

confidence: 83%

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Clarke

Samal

Pillus

2006

MBoC

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“…Interestingly binding to histone H3 K9 ac /K14 ac was found to be attenuated by phosphoryla-tion at serine 10 (pS10), a modification required for mitotic progression suggesting that this PTM can influence binding to the surrounding acetylation marks. Notably, pS10 has also been linked to increased HAT activity resulting in elevated levels of H3K14 ac [44].…”

Section: Bromodomain Substratesmentioning

confidence: 99%

The bromodomain interaction module

2012

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a b s t r a c t e-N-acetylation of lysine residues (K ac ) is one of the most abundant post-translation modifications (PTMs) in the human proteome. In the nucleus, acetylation of histones has been linked to transcriptional activation of genes but the functional consequences of most acetylation events and proteins recruited to these sites remains largely unknown. Bromodomains (BRDs) are small helical interaction modules that specifically recognize acetylation sites in proteins. BRDs have recently emerged as interesting targets for the development of specific protein interaction inhibitors, enabling a novel exiting strategy for the development of new therapies. This review provides an overview over sequence requirements of BRDs, known substrates and the structural mechanisms of specific K ac recognition.

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“…Traditionally, immunoassay methodologies such as immunoprecipitation, Western-Blotting, and immunofluorescence have dominated the biologists' toolbox for the characterization of histones and their PTMs [4][5][6]. However, these approaches have disadvantages that limit their application.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography mass spectrometry profiling of histones

Jacob

Amunugama

et al. 2007

Journal of Chromatography B

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Here we describe the use of reverse-phase liquid chromatography mass spectrometry (RP-LC-MS) to simultaneously characterize variants and post-translationally modified isoforms for each histone. The analysis of intact proteins significantly reduces the time of sample preparation and simplifies data interpretation. LC-MS analysis and peptide mass mapping have previously been applied to identify histone proteins and to characterize their post-translational modifications. However, these studies provided limited characterization of both linker histones and core histones. The current LC-MS analysis allows for the simultaneous observation of all histone PTMs and variants (both replacement and bulk histones) without further enrichment, which will be valuable in comparative studies. Protein identities were verified by the analysis of histone H2A species using RPLC fractionation, AU-PAGE separation and nano-LC-MS/MS.

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Phosphorylation of Serine 10 in Histone H3 Is Functionally Linked In Vitro and In Vivo to Gcn5-Mediated Acetylation at Lysine 14

Cited by 515 publications

References 59 publications

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

Distinct Roles for the Essential MYST Family HAT Esa1p in Transcriptional Silencing

The bromodomain interaction module

Liquid chromatography mass spectrometry profiling of histones

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