Acetylation Increases the α-Helical Content of the Histone Tails of the Nucleosome

Wang, Xiaoying; Moore, Susan C.; Laszckzak, Mario; Ausió, Juan

doi:10.1074/jbc.m004998200

Cited by 155 publications

(183 citation statements)

References 64 publications

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“…S2 and S3). Some of the qualitative trends of the conformational changes upon acetylation of LYS-16, observed from simulations, is consistent with the prior CD experiments, which reported steady increase in the alpha helical content of the H4 tails as a function of the number of added acetyl groups (35,36). Next, we probed the impact of the H4 tail acetylation on the DNA binding propensity.…”

supporting

confidence: 73%

Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation

Potoyan

Papoian

2012

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

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Intrinsically disordered proteins (IDP) are a broad class of proteins with relatively flat energy landscapes showing a high level of functional promiscuity, which are frequently regulated through posttranslational covalent modifications. Histone tails, which are the terminal segments of the histone proteins, are prominent IDPs that are implicated in a variety of signaling processes, which control chromatin organization and dynamics. Although a large body of work has been done on elucidating the roles of posttranslational modifications in functional regulation of IDPs, molecular mechanisms behind the observed behaviors are not fully understood. Using extensive atomistic molecular dynamics simulations, we found in this work that H4 tail mono-acetylation at LYS-16, which is a key covalent modification, induces a significant reorganization of the tail's conformational landscape, inducing partial ordering and enhancing the propensity for alpha-helical segments. Furthermore, our calculations of the potentials of mean force between the H4 tail and a DNA fragment indicate that contrary to the expectations based on simple electrostatic reasoning, the Lys-16 monoacetylated H4 tail binds to DNA stronger than the unacetylated protein. Based on these results, we propose a molecular mechanism for the way Lys-16 acetylation might lead to experimentally observed disruption of compact chromatin fibers.histone tails | atomistic simulations | polyelectrolytes

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supporting

confidence: 73%

Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation

Potoyan

Papoian

2012

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

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“…30 Indeed, studies have shown that a proportion of the histone tails adopt a helical formation, even when dissociated from nucleosomal DNA. 31 It is interesting to speculate that a similar conformation is produced by the H2A peptide or full-length protein when incubated with equimolar amounts of anionic bio-5 0 -AMP.…”

Section: Discussionmentioning

confidence: 99%

Nonenzymatic biotinylation of histone H2A

et al. 2009

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Holocarboxylase synthetase (HCS, eukaryotic enzyme) and BirA (prokaryotic) are biotin protein ligases that catalyze the ATP-dependent attachment of biotin to apocarboxylases via the reactive intermediate, bio-5 0 -AMP. In this study, we examined the in vitro mechanism of biotin attachment to histone H2A in the presence of HCS and BirA. The experiment derives from our observations that HCS is found in the nucleus of cells in addition to the cytoplasm, and it has the ability to attach biotin to histones in vitro (Narang et al., Hum Mol Genet 2004; 13:15-23). Using recombinant HCS or BirA, the rate of biotin attachment was considerably slower with histone H2A than with the biotin binding domain of an apocarboxylase. However, on incubation of recombinant H2A with chemically synthesized bio-5 0 -AMP, H2A was observed to be rapidly labeled with biotin in the absence of enzyme. Nonenzymatic biotinylation of a truncated apocarboxylase (BCCP87) has been previously reported (Streaker and Beckett, Protein Sci 2006; 15:1928-1935), though at a much slower rate than we observe for H2A. The specific attachment sites of nonenzymatically biotinylated recombinant H2A at different time points were identified using mass spectrometry, and were found to consist of a similar pattern of biotin attachment as seen in the presence of HCS, with preference for lysines in the highly basic N-terminal region of the histone. None of the lysine sites within H2A resembles the biotin attachment consensus sequence seen in carboxylases, suggesting a novel mechanism for histone biotinylation.

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“…In addition, evidence suggests that these domains also participate in protein-protein interactions between histones in the fully condensed chromatin fiber (3,7,16). Despite the perception of the tails as being "unstructured," biochemical and biophysical studies indicate they adopt defined structures and make specific interactions in chromatin (17)(18)(19)(20). The tail domains are not required for assembling or maintaining the structure of the nucleosome core and removal of the tails results in only marginal changes in the hydrodynamic shape, stability, and DNA wrapping within the nucleosome (21)(22)(23).…”

mentioning

confidence: 99%

Intra- and Inter-nucleosomal Protein-DNA Interactions of the Core Histone Tail Domains in a Model System

Zheng

Hayes

2003

Journal of Biological Chemistry

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The core histone tail domains are key regulators of eukaryotic chromatin structure and function and alterations in the tail-directed folding of chromatin fibers and higher order structures are the probable outcome of much of the post-translational modifications occurring in these domains. The functions of the tail domains are likely to involve complex intra-and inter-nucleosomal histone-DNA interactions, yet little is known about either the structures or interactions of these domains. Here we introduce a method for examining inter-nucleosome interactions of the tail domains in a model dinucleosome and determine the propensity of each of the four N-terminal tail domains to mediate such interactions in this system. Using a strong nucleosome "positioning" sequence, we reconstituted a nucleosome containing a single histone site specifically modified with a photoinducible cross-linker within the histone tail domain, and a second nucleosome containing a radiolabeled DNA template. These two nucleosomes were then ligated together and cross-linking induced by brief UV irradiation under various solution conditions. After cross-linking, the two templates were again separated so that cross-linking representing inter-nucleosomal histone-DNA interactions could be unambiguously distinguished from intra-nucleosomal cross-links. Our results show that the N-terminal tails of H2A and H2B, but not of H3 and H4, make internucleosomal histone-DNA interactions within the dinucleosome. The relative extent of intra-to inter-nucleosome interactions was not strongly dependent on ionic strength. Additionally, we find that binding of a linker histone to the dinucleosome increased the association of the H3 and H4 tails with the linker DNA region.

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Acetylation Increases the α-Helical Content of the Histone Tails of the Nucleosome

Cited by 155 publications

References 64 publications

Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation

Regulation of the H4 tail binding and folding landscapes via Lys-16 acetylation

Nonenzymatic biotinylation of histone H2A

Intra- and Inter-nucleosomal Protein-DNA Interactions of the Core Histone Tail Domains in a Model System

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