Identification of novel histone post-translational modifications by peptide mass fingerprinting.
The extent and pattern of histone post-translational modifications is a key determinant dictating the structure of chromatin. We employed mass spectrometry to map the post-translational modifications present on mammalian core histones. Using accurate peptide mass fingerprinting on proteolytic digests of purified histones, we identified more than 20 novel sites of histone modification. One newly identified site of methylation, histone H4 lysine 59, maps to the surface of the nucleosome in close proximity to the site of the only identified histone core modification, histone H3 lysine 79. Consistent with the role of histone H3 lysine 79 methylation in the formation of silent chromatin structure, histone H4 lysine 59 is essential for transcriptional silencing at the yeast silent mating loci and telomeres.
Zhang
Liwen
L
Department of Chemistry, The Ohio State University, Columbus, OH 43210, USA.
Eugeni
Ericka E
EE
Parthun
Mark R
MR
Freitas
Michael A
MA
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002843:Chromatin / Q000737:chemistry; D018360:Crystallography, X-Ray; D019175:DNA Methylation; D020868:Gene Silencing; D006657:Histones / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D013058:Mass Spectrometry; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D009707:Nucleosomes / Q000737:chemistry; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D010449:Peptide Mapping; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics; D016615:Telomere / Q000235:genetics; D014357:Trypsin / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D010446:Peptide Fragments; D014357:Trypsin; D010434:Pepsin A; D000409:Alanine