Systems Level Analysis of Histone H3 Post-translational Modifications (PTMs) Reveals Features of PTM Crosstalk in Chromatin Regulation
| Autor: | Chung-Fan Lee, Ole N. Jensen, Veit Schwämmle, Xudong Wu, Simone Sidoli, Kristian Helin, Chrystian Ruminowicz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Proteomics
0301 basic medicine Histone-modifying enzymes Computational biology Biology Arginine Methylation Biochemistry Analytical Chemistry Histones Gene Knockout Techniques Mice 03 medical and health sciences Histone H3 Tandem Mass Spectrometry Journal Article Animals Histone code Molecular Biology Polycomb Repressive Complex 1 Genetics Research Lysine Polycomb Repressive Complex 2 Mouse Embryonic Stem Cells Chromatin Crosstalk (biology) 030104 developmental biology Histone Histone methyltransferase biology.protein PRC2 Protein Processing Post-Translational Chromatography Liquid |
| Zdroj: | Schwämmle, V, Sidoli, S, Ruminowicz, C, Wu, X, Lee, C-F, Helin, K & Jensen, O N 2016, ' Systems Level Analysis of Histone H3 Post-translational Modifications (PTMs) Reveals Features of PTM Crosstalk in Chromatin Regulation ', Molecular and Cellular Proteomics, vol. 15, no. 8, pp. 2715-2729 . https://doi.org/10.1074/mcp.M115.054460 |
| DOI: | 10.1074/mcp.M115.054460 |
| Popis: | Histones are abundant chromatin constituents carrying numerous post-translational modifications (PTMs). Such PTMs mediate a variety of biological functions, including recruitment of enzymatic readers, writers and erasers that modulate DNA replication, transcription and repair. Individual histone molecules contain multiple coexisting PTMs, some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. Here, we present an integrated experimental and computational systems level molecular characterization of histone PTMs and PTM crosstalk. Using wild type and engineered mouse embryonic stem cells (mESCs) knocked out in components of the Polycomb Repressive Complex 2 (PRC2, Suz12(-/-)), PRC1 (Ring1A/B(-/-)) and (Dnmt1/3a/3b(-/-)) we performed comprehensive PTM analysis of histone H3 tails (50 aa) by utilizing quantitative middle-down proteome analysis by tandem mass spectrometry. We characterized combinatorial PTM features across the four mESC lines and then applied statistical data analysis to predict crosstalk between histone H3 PTMs. We detected an overrepresentation of positive crosstalk (codependent marks) between adjacent mono-methylated and acetylated marks, and negative crosstalk (mutually exclusive marks) among most of the seven characterized di- and tri-methylated lysine residues in the H3 tails. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites, including H3R2me, H3R8me and H3K37me. Integration of the H3 data with RNAseq data by coabundance clustering analysis of histone PTMs and histone modifying enzymes revealed correlations between PTM and enzyme levels. We conclude that middle-down proteomics is a powerful tool to determine conserved or dynamic interdependencies between histone marks, which paves the way for detailed investigations of the histone code. Histone H3 PTM data is publicly available in the CrossTalkDB repository at http://crosstalkdb.bmb.sdu.dk. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|