Profiling of Histone Post-Translational Modifications in Mouse Brain with High-Resolution Top-Down Mass Spectrometry

As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (...

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Veröffentlicht in:Journal of proteome research Jg. 16; H. 2; S. 599
Hauptverfasser: Zhou, Mowei, Paša-Tolić, Ljiljana, Stenoien, David L
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 03.02.2017
Schlagworte:
Algorithms
Amino Acid Sequence - genetics
Animals
Brain - metabolism
Computational Biology
Histones - genetics
Histones - metabolism
Mass Spectrometry
Mice
Protein Processing, Post-Translational - genetics
Proteome - genetics
top-down mass spectrometry
histones
post-translational modifications
ISSN:1535-3907, 1535-3907
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Zusammenfassung:As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms. Here we used state-of-the-art mass spectrometry and a bioinformatics workflow for targeted data analysis and visualization. The workflow uses ProMex for intact mass deconvolution, MSPathFinder as a search engine, and LcMsSpectator as a data visualization tool. When complemented with the open-modification tool TopPIC, this workflow enabled identification of novel histone PTMs including tyrosine bromination on histone H4 and H2A, H3 glutathionylation, and mapping of conventional PTMs along the entire protein for many histone subunits.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1535-3907
1535-3907
DOI:10.1021/acs.jproteome.6b00694