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Chromatin Central: towards the comparative proteome by accurate mapping of the yeast proteomic environment

Anna Shevchenko1, Assen Roguev23, Daniel Schaft2, Luke Buchanan2, Bianca Habermann1, Cagri Sakalar2, Henrik Thomas1, Nevan J Krogan3, Andrej Shevchenko1* and A Francis Stewart3*

Author Affiliations

1 MPI of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany

2 Genomics, BioInnovationsZentrum, Technische Universität Dresden, Am Tatzberg 47-51, 01307 Dresden, Germany

3 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158, USA

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Genome Biology 2008, 9:R167  doi:10.1186/gb-2008-9-11-r167

Published: 28 November 2008

Abstract

Background

Understanding the design logic of living systems requires the understanding and comparison of proteomes. Proteomes define the commonalities between organisms more precisely than genomic sequences. Because uncertainties remain regarding the accuracy of proteomic data, several issues need to be resolved before comparative proteomics can be fruitful.

Results

The Saccharomyces cerevisiae proteome presents the highest quality proteomic data available. To evaluate the accuracy of these data, we intensively mapped a proteomic environment, termed 'Chromatin Central', which encompasses eight protein complexes, including the major histone acetyltransferases and deacetylases, interconnected by twelve proteomic hyperlinks. Using sequential tagging and a new method to eliminate background, we confirmed existing data but also uncovered new subunits and three new complexes, including ASTRA, which we suggest is a widely conserved aspect of telomeric maintenance, and two new variations of Rpd3 histone deacetylase complexes. We also examined the same environment in fission yeast and found a very similar architecture based on a scaffold of orthologues comprising about two-thirds of all proteins involved, whereas the remaining one-third is less constrained. Notably, most of the divergent hyperlinks were found to be due to gene duplications, hence providing a mechanism for the fixation of gene duplications in evolution.

Conclusions

We define several prerequisites for comparative proteomics and apply them to examine a proteomic environment in unprecedented detail. We suggest that high resolution mapping of proteomic environments will deliver the highest quality data for comparative proteomics.