Dataset Information

EpiProfile 2.0: a proteomics tool to quantify histone modifications by mass spectrometry

ABSTRACT: The histone LC-MS/MS data analysis is challenging due to the large number and variety of isobaric histone peptides, and the high dynamic range of histone peptide abundances. We introduce EpiProfile 2.0 to quantify histone post-translational modifications from mass spectrometry data, in which fragment ions are used to determine the retention time of peptides and discriminate isobaric peptides. EpiProfile can automatically recognize and efficiently process both data-dependent and data-independent acquisition runs (DDA and DIA), and high-resolution and low-resolution instrument runs. The proteomics tool was tested on human cells and validated by synthetic histone peptides. EpiProfile is the first automatic program to determine the retention time and discriminate isobaric peptides for histone modifications with DIA MS.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Hela Cell

DISEASE(S): Cervix Carcinoma

SUBMITTER: Zuo-Fei Yuan

LAB HEAD: Benjamin A. Garcia

PROVIDER: PXD004166 | Pride | 2018-05-29

REPOSITORIES: Pride

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Publications

EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data.

Yuan Zuo-Fei ZF Sidoli Simone S Marchione Dylan M DM Simithy Johayra J Janssen Kevin A KA Szurgot Mary R MR Garcia Benjamin A BA

Journal of proteome research 20180530 7

Epigenetics has become a fundamental scientific discipline with various implications for biology and medicine. Epigenetic marks, mostly DNA methylation and histone post-translational modifications (PTMs), play important roles in chromatin structure and function. Accurate quantification of these marks is an ongoing challenge due to the variety of modifications and their wide dynamic range of abundance. Here we present EpiProfile 2.0, an extended version of our 2015 software (v1.0), for accurate q ...[more]

PMID: 29790754

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Project description:Chromatin structure and function is maintained by dynamic protein-protein and protein-nucleic acid interactions. Histones are a family of proteins that are abundant chromatin constituents and that carry numerous post-translational modifications (PTMs). Histone PTMs mediate a variety of biological activities, including recruitment of enzymatic readers, writers and erasers that modulate protein activities, DNA replication, transcription and repair. Individual histone molecules contain multiple co-existing PTMs some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. We here present an integrated experimental and computational approach for systems level molecular characterization of PTMs and PTM crosstalk. Using wildtype and engineered mouse embryonic stem cells with perturbations in the Polycomb Repressive Complex 1 (PRC1, suz12-/-), PRC2 (Ring1A/b-/-) and DNA methyltransferases (Dnmt1/3a/3b-/-) we performed comprehensive PTM analysis of histone H3 tails. We identified unique histone H3 PTM features of each of the four cell lines and we detected common combinatorial PTM features across cell lines. Using quantitative middle-down proteomics combined with probabilistic and statistical data analysis we extracted histone H3 PTM profiles for all four mESC systems. PTM crosstalk emerged as mutually exclusive histone PTMs or coordinately regulated PTMs independent of histone peptide abundance in the four model systems. We detected positive crosstalk between adjacent mono-methylated marks but strong negative crosstalk among most of the seven characterized di- and tri-methylations on lysines. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites in histone H3, including H3R2me, H3R8me and H3K37me, which exhibited specific PTM codes suggesting a particular role in chromatin. All histone H3 PTM data is available in our publicly available CrossTalkDB repository at http://crosstalkdb.bmb.sdu.dk

Dataset Information

EpiProfile 2.0: a proteomics tool to quantify histone modifications by mass spectrometry

Publications

EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data.

Similar Datasets

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