Site-specific acetylation of ISWI by GCN5

Ferreira, Roger; Eberharter, Anton; Bonaldi, Tiziana; Chioda, Mariacristina; Imhof, Axel; Becker, Peter B.

doi:10.1186/1471-2199-8-73

Cited by 42 publications

(36 citation statements)

References 31 publications

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“…Regulation of chromatin remodelers by acetylation is not limited to the Swi/ Snf type complexes; the Drosophila ISWI ATPase can be acetylated by the Gcn5 and p300 acetyltransferases on lysine 753, a region of the protein that bears similarity to the H3 tail (Ferreira et al 2007). These examples show that acetylation may serve to regulate the properties of both components of nucleosome remodeling reaction, the nucleosome substrate, and the remodeling enzyme.…”

Section: Regulation Of Remodelers By Posttranslational Modificationmentioning

confidence: 99%

Nucleosome Remodeling and Epigenetics

Becker

Workman

2013

Cold Spring Harbor Perspectives in Biology

262

203

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Section: Regulation Of Remodelers By Posttranslational Modificationmentioning

confidence: 99%

Nucleosome Remodeling and Epigenetics

Becker

Workman

2013

Cold Spring Harbor Perspectives in Biology

262

203

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“…Gcn5-the acetyltransferase in SAGA, SLIK, and ADA complexes (Lee and Workman 2007)-regulates activity of the RSC complex during replication stress by acetylation of the Rsc4 subunit (VanDemark et al 2007;Charles et al 2011). Also, Gcn5 acetylates ISWI in Drosophila (Ferreira et al 2007) and proliferator g coactivator 1 (PGC-1) in mammals (Lerin et al 2006). More recently, we showed that Snf2, the catalytic subunit of Swi/Snf, is acetylated by Gcn5 (Kim et al 2010).…”

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confidence: 99%

Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions

et al. 2014

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The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why such mechanisms are required to enhance Swi/Snf activity on nucleosomes. Snf2, the catalytic subunit of the Swi/Snf remodeling complex, has been shown to be a target of the Gcn5 acetyltransferase. Our study found that acetylation of Snf2 regulates both recruitment and release of Swi/Snf from stress-responsive genes. Also, the intramolecular interaction of the Snf2 bromodomain with the acetylated lysine residues on Snf2 negatively regulates binding and remodeling of acetylated nucleosomes by Swi/Snf. Interestingly, the presence of transcription activators mitigates the effects of the reduced affinity of acetylated Snf2 for acetylated nucleosomes. Supporting our in vitro results, we found that activator-bound genes regulating metabolic processes showed greater retention of the Swi/Snf complex even when Snf2 was acetylated. Our studies demonstrate that competing effects of (1) Swi/Snf retention by activators or high levels of histone acetylation and (2) Snf2 acetylation-mediated release regulate dynamics of Swi/Snf occupancy at target genes.

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“…Point mutations of the Rsc4 acetylation site display only mild phenotypes. Another chromatin-remodeling enzyme, Drosophila ISWI, has been shown similarly to be an in vivo and in vitro target of Gcn5 (10). However, the biological role of this acetylation mark also is unknown.…”

mentioning

confidence: 99%

Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress

Charles¹,

Chen²,

Shih³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Recent work has identified several posttranslational modifications (PTMs) on chromatin-remodeling complexes. Compared with our understanding of histone PTMs, significantly less is known about the functions of PTMs on remodeling complexes, because identification of their specific roles often is hindered by the presence of redundant pathways. Remodels the Structure of Chromatin (RSC) is an essential, multifunctional ATP-dependent chromatin-remodeling enzyme of Saccharomyces cerevisiae that preferentially binds acetylated nucleosomes. RSC is itself acetylated by Gcn5 on lysine 25 (K25) of its Rsc4 subunit, adjacent to two tandem bromodomains. It has been shown that an intramolecular interaction between the acetylation mark and the proximal bromodomain inhibits binding of the second bromodomain to acetylated histone H3 tails. We report here that acetylation does not significantly alter the catalytic activity of RSC or its ability to recognize histone H3-acetylated nucleosomes preferentially in vitro. However, we find that Rsc4 acetylation is crucial for resistance to DNA damage in vivo. Epistatic miniarray profiling of the rsc4-K25R mutant reveals an interaction with mutants in the INO80 complex, a mediator of DNA damage and replication stress tolerance. In the absence of a core INO80 subunit, rsc4-K25R mutants display sensitivity to hydroxyurea and delayed S-phase progression under DNA damage. Thus, Rsc4 helps promote resistance to replication stress, and its single acetylation mark regulates this function. These studies offer an example of acetylation of a chromatin-remodeling enzyme controlling a biological output of the system rather than regulating its core enzymatic properties. R egulation of DNA accessibility within chromatin is enabled by the combined action of ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes. Histone-modifying enzymes introduce covalent posttranslational modifications (PTMs) at specific locations. These PTMs either affect chromatin conformation directly or act as a signal for the recruitment of specific factors (1). ATP-dependent chromatin-remodeling complexes noncovalently alter chromatin conformation and composition using the energy of ATP (2). Intriguingly, these complexes also contain several different PTMs including acetylation and phosphorylation (2). However, compared with the functional effects of PTMs on histones, the functional effects of these PTMs are less well understood.Subunits of ATP-dependent chromatin-remodeling complexes often contain domains capable of recognizing specific PTMs. This phenomenon has been best studied in the context of histone tail acetylation, which is recognized by protein modules, called "bromodomains" (1, 2). In the SWI/SNF subfamily of remodelers, many subunits contain bromodomains (2), which have been shown to facilitate recruitment of these complexes to acetylated nucleosomes (3-7). Recent work has shown that bromodomains can bind acetylation marks in cis. Specifically, an acetylation mark on Rsc4, a subunit of RSC, the maj...

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Site-specific acetylation of ISWI by GCN5

Cited by 42 publications

References 31 publications

Nucleosome Remodeling and Epigenetics

Nucleosome Remodeling and Epigenetics

Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions

Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress

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