Heterochromatin protein 1 is extensively decorated with histone code-like post-translational modifications.
Heterochromatin protein 1 (HP1) family members (alpha, beta, and gamma) bind histone H3 methylated at Lys-9, leading to gene silencing and heterochromatin formation. Several previous reports have suggested that HP1s are post-translationally 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.
LeRoy
Gary
G
Department Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Weston
John T
JT
Zee
Barry M
BM
Young
Nicolas L
NL
Plazas-Mayorca
Mariana D
MD
Garcia
Benjamin A
BA
D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D004330:Drosophila; D006657:Histones / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D010455:Peptides; D020033:Protein Isoforms; D000090266:Chromobox Protein Homolog 5