Formaldehyde-Induced Histone Modifications <i>in Vitro</i>

Lü, Kun; Boysen, Gunnar; Gao, Lina; Collins, Leonard B.; Swenberg, James A.

doi:10.1021/tx8000576

Cited by 37 publications

(42 citation statements)

References 22 publications

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“…2D), suggesting that acetylated histones may prevent sites from being targeted by Acr. Consistent with this result, formaldehyde reacted only with unmodified and not acetylated histone H4, and the formation of formaldehyde-lysine adducts prevented those sites from being properly modified in vitro (39). Thus, protecting chromatin from being attacked by environmental factors, such as aldehydes, may represent a novel function of histone PTMs.…”

Section: Discussionsupporting

confidence: 53%

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Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation

Chen

Fang

et al. 2013

Journal of Biological Chemistry

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Background:The epigenetic effect of acrolein, an ␣,␤-unsaturated aldehyde, remains unclear. Results: Acrolein specifically inhibits acetylations of N-terminal tails of cytosolic but not nuclear histones and reduces their delivery into chromatin. Conclusion: Acrolein differentially affects post-translational modifications of free histones and nucleosomal histones and compromises chromatin assembly. Significance: Affecting chromatin assembly may represent a new model for the interaction between environmental factors and the genome function.

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Section: Discussionsupporting

confidence: 53%

“…Acr Drastically Down-regulates Levels of N-terminal Tail Acetylations of Cytosolic Histones-Formaldehyde-modified histones are resistant to PTMs in vitro (39). Because Acr reacts with histone lysine residues ( Figs.…”

Section: Acr-histone Adduct Formation In Vitro and In Vivo-tomentioning

confidence: 99%

Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation

Chen

Fang

et al. 2013

Journal of Biological Chemistry

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“…3). The results are in agreement with those seen upon formaldehyde exposure of recombinant histone H4 (60). These data support the idea that the observed reduction of H4K12 acetylation and probably H3K9&14 acetylations in cells exposed to Acr may occur because of the formation of Acr-lysine adducts.…”

Section: Discussionsupporting

confidence: 90%

Mechanisms Underlying Acrolein-Mediated Inhibition of Chromatin Assembly

Fang

Chen

et al. 2016

Molecular and Cellular Biology

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Acrolein is a major component of cigarette smoke and cooking fumes. Previously, we reported that acrolein compromises chromatin assembly; however, underlying mechanisms have not been defined. Here, we report that acrolein reacts with lysine residues, including lysines 5 and 12, sites important for chromatin assembly, on histone H4 in vitro and in vivo. Acrolein-modified histones are resistant to acetylation, suggesting that the reduced H4K12 acetylation that occurs following acrolein exposure is probably due to the formation of acrolein-histone lysine adducts. Accordingly, the association of H3/H4 with the histone chaperone ASF1 and importin 4 is disrupted and the translocation of green fluorescent protein-tagged H3 is inhibited in cells exposed to acrolein. Interestingly, in vitro plasmid supercoiling assays revealed that treatment of either histones or ASF1 with acrolein has no effect on the formation of plasmid supercoiling, indicating that acrolein-protein adduct formation itself does not directly interfere with nucleosome assembly. Notably, exposure of histones to acrolein prior to histone acetylation leads to the inhibition of remodeling and spacing factor chromatin assembly, which requires acetylated histones for efficient assembly. These results suggest that acrolein compromises chromatin assembly by reacting with histone lysine residues at the sites critical for chromatin assembly and prevents these sites from physiological modifications.

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“…The formylation of proteins can occur in sample preparation by the use of formaldehyde described under "Experimental Procedures" (39) or gel silver staining protocols (40), and by using excessive formic acid (41). Thus, we did not use any of these reagents in any of our preparations.…”

Section: Discussionmentioning

confidence: 99%

Heterochromatin Protein 1 Is Extensively Decorated with Histone Code-like Post-translational Modifications

LeRoy

Weston

Zee

et al. 2009

Molecular & Cellular Proteomics

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Heterochromatin protein 1 (HP1) family members (␣, ␤, and ␥) bind histone H3 methylated at Lys-9, leading to gene silencing and heterochromatin formation. Several previous reports have suggested that HP1s are posttranslationally modified, yet sites of modification have not yet been exhaustively determined. Here we perform the first comprehensive proteomic analysis of all HP1 isoforms using tandem mass spectrometry. Our data reveal that all HP1 isoforms are highly modified in a manner analogous to histones including phosphorylation, acetylation, methylation, and formylation, including several sites having multiple different types of modifications. Additionally, many of these modifications are found in both the chromo-and chromoshadow domains, suggesting that they may have an important role in modulating HP1 interactions or functions. These studies are the first to systematically map the abundant sites of covalent modifications on HP1 isoforms and provide the foundation for future investigations to test whether these modifications are essential in heterochromatin maintenance or other nuclear processes. Molecular & Cellular Proteomics 8: 2432-2442, 2009.The mammalian HP1␣, ␤, and ␥ proteins are a family of chromatin-associated proteins that are homologs of the Drosophila heterochromatin protein 1 (HP1) 1 , originally identified as a protein required for position effect variegation. Position effect variegation is the silencing phenomenon that occurs when a block of euchromatin is placed adjacent to a region of heterochromatin (1). HP1␣, ␤, and ␥ proteins all contain a N-terminal chromodomain (CD) and a C-terminal chromoshadow domain (CSD) that are linked together by a flexible hinge region (2). The CD in HP1 is one of many specialized domains found in a number of other chromatin-associated proteins that recognizes histone post-translational modifications (PTMs). In particular, x-ray crystallographic studies have demonstrated that the HP1 chromodomain binds directly to the histone H3 protein trimethylated on Lys-9 (3).The C-terminal CSD domain is structurally similar to the CD and is thought to be responsible for dimerization and interactions with other proteins. The mammalian HP1␣, ␤, and ␥ proteins have been shown to form both homo-and heterodimers with each other (4). Although the HP1␣, ␤, and ␥ proteins have similar structures and dimerize with each other, studies suggest they have non-overlapping functions. As the name implies, the HP1 proteins are generally associated with constitutive heterochromatic loci; however, HP1␥ localizes with both hetero-and euchromatin (5). Moreover, although microscopy analysis has demonstrated that HP1␣ and HP1␤ localize together at many heterochromatic loci, they do not completely overlap, further suggesting that they can function independently (6). Furthermore, HP1␥ was found to be associated with the DNA of actively transcribed genes by chromatin immunoprecipitation (7).All three of the mammalian HP1 proteins can complex with the co-repressor protein, KAP-1/Tif1␤. Interestingly,...

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Formaldehyde-Induced Histone Modifications in Vitro

Cited by 37 publications

References 22 publications

Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation

Cigarette Smoke Component Acrolein Modulates Chromatin Assembly by Inhibiting Histone Acetylation

Mechanisms Underlying Acrolein-Mediated Inhibition of Chromatin Assembly

Heterochromatin Protein 1 Is Extensively Decorated with Histone Code-like Post-translational Modifications

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