TY - JOUR
T1 - Long-distance combinatorial linkage between methylation and acetylation on histone H3 N termini
AU - Taverna, Sean D.
AU - Ueberheide, Beatrix M.
AU - Liu, Yifan
AU - Tackett, Alan J.
AU - Dias, Robert L.
AU - Shabanowitz, Jeffrey
AU - Chait, Brian T.
AU - Hunt, Donald F.
AU - Allis, C. David
PY - 2007/2/13
Y1 - 2007/2/13
N2 - Individual posttranslational modifications (PTMs) on histones have well established roles in certain biological processes, notably transcriptional programming. Recent genomewide studies describe patterns of covalent modifications, such as H3 methylation and acetylation at promoters of specific target genes, or "bivalent domains," in stem cells, suggestive of a possible combinatorial interplay between PTMs on the same histone. However, detection of long-range PTM associations is often problematic in antibody-based or traditional mass spectrometric-based analyses. Here, histone H3 from a ciliate model was analyzed as an enriched source of transcriptionally active chromatin. Using a recently developed mass spectrometric approach, combinatorial modification states on single, long N-ternminal H3 fragments (residues 1-50) were determined. The entire modification status of intact N termini was obtained and indicated correlations between K4 methylation and H3 acetylation. In addition, K4 and K27 methylation were identified concurrently on one H3 species. This methodology is applicable to other histones and larger polypeptides and will likely be a valuable tool in understanding the roles of combinatorial patterns of PTMs.
AB - Individual posttranslational modifications (PTMs) on histones have well established roles in certain biological processes, notably transcriptional programming. Recent genomewide studies describe patterns of covalent modifications, such as H3 methylation and acetylation at promoters of specific target genes, or "bivalent domains," in stem cells, suggestive of a possible combinatorial interplay between PTMs on the same histone. However, detection of long-range PTM associations is often problematic in antibody-based or traditional mass spectrometric-based analyses. Here, histone H3 from a ciliate model was analyzed as an enriched source of transcriptionally active chromatin. Using a recently developed mass spectrometric approach, combinatorial modification states on single, long N-ternminal H3 fragments (residues 1-50) were determined. The entire modification status of intact N termini was obtained and indicated correlations between K4 methylation and H3 acetylation. In addition, K4 and K27 methylation were identified concurrently on one H3 species. This methodology is applicable to other histones and larger polypeptides and will likely be a valuable tool in understanding the roles of combinatorial patterns of PTMs.
KW - Bivalent domain
KW - Electron transfer dissociation
KW - Mass spectrometry
KW - Posttranslational modifications
KW - Tetrahymena
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U2 - 10.1073/pnas.0610993104
DO - 10.1073/pnas.0610993104
M3 - Article
C2 - 17284592
AN - SCOPUS:33847768829
SN - 0027-8424
VL - 104
SP - 2086
EP - 2091
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -