N ε -Formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function

Abstract

Post-translational modification of histones and other chromosomal proteins regulates chromatin conformation and gene activity. Methylation and acetylation of lysyl residues are among the most frequently described modifications in these proteins. Whereas these modifications have been studied in detail, very little is known about a recently discovered chemical modification, the Nε-lysine formylation, in histones and other nuclear proteins. Here we mapped, for the first time, the sites of lysine formylation in histones and several other nuclear proteins. We found that core and linker histones are formylated at multiple lysyl residues located both in the tails and globular domains of histones. In core histones, formylation was found at lysyl residues known to be involved in organization of nucleosomal particles that are frequently acetylated and methylated. In linker histones and high mobility group proteins, multiple formylation sites were mapped to residues with important role in DNA binding. Nε-lysine formylation in chromosomal proteins is relatively abundant, suggesting that it may interfere with epigenetic mechanisms governing chromatin function, which could lead to deregulation of the cell and disease.

Quantitative Mass Spectrometry of Histones H3.2 and H3.3 in Suz12-deficient Mouse Embryonic Stem Cells Reveals Distinct, Dynamic Post-translational Modifications at Lys-27 and Lys-36

“…A more detailed characterization of the functional role of H3K27ac in regulating polycomb group target gene expression in mouse ESCs will be described separately. 2 The mass spectrometry data provided a much more detailed overview of the modification profiles of Lys-27/Lys-36 than was possible with standard Western blotting approaches. For example, K36me2 was identified with K27(unmodified) and K27me1, -me2, -me3, and -ac.…”

“…Histones can be extensively modified, and various post-translational modifications (PTMs) 1 of histones have been reported, including phosphorylation (ph), mono-(me1), di-(me2), trimethylation (me3), acetylation (ac), formylation, citrullination, and ubiquitylation (1)(2)(3). Most histone PTMs are located within the N-terminal tails of histones, which contain several basic residues such as lysines and arginines.…”

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

“…6B). Formylation of proteins has recently emerged as an in vivo covalent modification on histones and other nuclear proteins (28,29), and these findings will fuel future work on the subject in the context of its importance in epigenetic silencing through nuclear-or chromatin-mediated pathways.…”

Lysine Propionylation Is a Prevalent Post-translational Modification in Thermus thermophilus

“…Other types of lysine acylations have been described recently, such as formylation (23,24), propionylation (25), butyrylation (25), and crotonylation (26) in histones and other types of proteins. Lysine propionylation was initially reported in histones (25), but subsequently three non-histone proteins (p53, p300, and CREB-binding protein) were shown to be propionylated (27)(28)(29)(30).…”