PTMViz: a tool for analyzing and visualizing histone post translational modification data

Abstract Background Histone post-translational modifications (PTMs) play an important role in our system by regulating the structure of chromatin and therefore contribute to the regulation of gene and protein expression. Irregularities in histone PTMs can lead to a variety of different diseases including various forms of cancer. Histone modifications are analyzed using high resolution mass spectrometry, which generate large amounts of data that requires sophisticated bioinformatics tools for analysis and visualization. PTMViz is designed for downstream differential abundance analysis and visualization of both protein and/or histone modifications. Results PTMViz provides users with data tables and visualization plots of significantly differentiated proteins and histone PTMs between two sample groups. All the data is packaged into interactive data tables and graphs using the Shiny platform to help the user explore the results in a fast and efficient manner to assess if changes in the system are due to protein abundance changes or epigenetic changes. In the example data provided, we identified several proteins differentially regulated in the dopaminergic pathway between mice treated with methamphetamine compared to a saline control. We also identified histone post-translational modifications including histone H3K9me, H3K27me3, H4K16ac, and that were regulated due to drug exposure. Conclusions Histone modifications play an integral role in the regulation of gene expression. PTMViz provides an interactive platform for analyzing proteins and histone post-translational modifications from mass spectrometry data in order to quickly identify differentially expressed proteins and PTMs.

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A G(enomic)P(ositioning)S(ystem) for Plant RNAPII Transcription

10.20944/preprints202003.0290.v1 ◽

2020 ◽

Author(s):

Sebastian Marquardt ◽

Xueyuan Leng ◽

Quentin Thomas ◽

Simon Rasmussen

Keyword(s):

Gene Expression ◽

Histone Modifications ◽

Regulation Of Gene Expression ◽

Positioning System ◽

Biological Functions ◽

Post Translational Modifications ◽

Histone Ptms ◽

Definition Of ◽

Generation Sequencing ◽

Rnapii Transcription

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

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A mass spectrometry-based assay using metabolic labeling to rapidly monitor chromatin accessibility of modified histone proteins

Scientific Reports ◽

10.1038/s41598-019-49894-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Simone Sidoli ◽

Mariana Lopes ◽

Peder J. Lund ◽

Naomi Goldman ◽

Maria Fasolino ◽

...

Keyword(s):

Mass Spectrometry ◽

Chemical Properties ◽

Chromatin Accessibility ◽

Metabolic Labeling ◽

Post Translational Modifications ◽

Histone Ptms ◽

Active Transcription ◽

Or Gene ◽

Histone Codes

Abstract Histone post-translational modifications (PTMs) contribute to chromatin accessibility due to their chemical properties and their ability to recruit enzymes responsible for DNA readout and chromatin remodeling. To date, more than 400 different histone PTMs and thousands of combinations of PTMs have been identified, the vast majority with still unknown biological function. Identification and quantification of histone PTMs has become routine in mass spectrometry (MS) but, since raising antibodies for each PTM in a study can be prohibitive, lots of potential is lost from MS datasets when uncharacterized PTMs are found to be significantly regulated. We developed an assay that uses metabolic labeling and MS to associate chromatin accessibility with histone PTMs and their combinations. The labeling is achieved by spiking in the cell media a 5x concentration of stable isotope labeled arginine and allow cells to grow for at least one cell cycle. We quantified the labeling incorporation of about 200 histone peptides with a proteomics workflow, and we confirmed that peptides carrying PTMs with extensively characterized roles in active transcription or gene silencing were in highly or poorly labeled forms, respectively. Data were further validated using next-generation sequencing to assess the transcription rate of chromatin regions modified with five selected PTMs. Furthermore, we quantified the labeling rate of peptides carrying co-existing PTMs, proving that this method is suitable for combinatorial PTMs. We focus on the abundant bivalent mark H3K27me3K36me2, showing that H3K27me3 dominantly represses histone swapping rate even in the presence of the more permissive PTM H3K36me2. Together, we envision this method will help to generate hypotheses regarding histone PTM functions and, potentially, elucidate the role of combinatorial histone codes.

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Many Routes from Glycolysis to Histone PTMs. Nature “Matters Arising” response to: Zhang et al. Metabolic regulation of gene expression by histone lactylation. (2019) Nature. 574(7779), 575-580.

10.31219/osf.io/sba8j ◽

2020 ◽

Author(s):

Chaitanya A. Kulkarni ◽

Paul Brookes

Keyword(s):

Gene Expression ◽

Small Molecule ◽

Metabolic Regulation ◽

Regulation Of Gene Expression ◽

Histone Mark ◽

Acetyl Coa ◽

Post Translational Modifications ◽

Histone Ptms

Multiple histone post-translational modifications (PTMs) originate from small molecule metabolites (e.g. acetyl-lysine from acetyl-CoA) 1. As such, we read with interest the recent Nature paper from Zhang et al. 2 reporting discovery of lysine lactylation as a novel histone mark originating from the metabolite lactate. However, several concerns arise regarding the identity and source of this novel PTM.

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MatrisomeDB: the ECM-protein knowledge database

Nucleic Acids Research ◽

10.1093/nar/gkz849 ◽

2019 ◽

Vol 48 (D1) ◽

pp. D1136-D1144 ◽

Cited By ~ 20

Author(s):

Xinhao Shao ◽

Isra N Taha ◽

Karl R Clauser ◽

Yu (Tom) Gao ◽

Alexandra Naba

Keyword(s):

Mass Spectrometry ◽

Cell Polarization ◽

Mass Spectrometry Data ◽

Breast Cancers ◽

Complete Collection ◽

Post Translational Modifications ◽

Proteomic Data ◽

Tissue Organization ◽

Data Files ◽

Cancer Types

Abstract The extracellular matrix (ECM) is a complex and dynamic meshwork of cross-linked proteins that supports cell polarization and functions and tissue organization and homeostasis. Over the past few decades, mass-spectrometry-based proteomics has emerged as the method of choice to characterize the composition of the ECM of normal and diseased tissues. Here, we present a new release of MatrisomeDB, a searchable collection of curated proteomic data from 17 studies on the ECM of 15 different normal tissue types, six cancer types (different grades of breast cancers, colorectal cancer, melanoma, and insulinoma) and other diseases including vascular defects and lung and liver fibroses. MatrisomeDB (http://www.pepchem.org/matrisomedb) was built by retrieving raw mass spectrometry data files and reprocessing them using the same search parameters and criteria to allow for a more direct comparison between the different studies. The present release of MatrisomeDB includes 847 human and 791 mouse ECM proteoforms and over 350 000 human and 600 000 mouse ECM-derived peptide-to-spectrum matches. For each query, a hierarchically-clustered tissue distribution map, a peptide coverage map, and a list of post-translational modifications identified, are generated. MatrisomeDB is the most complete collection of ECM proteomic data to date and allows the building of a comprehensive ECM atlas.

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LuciPHOr2: site localization of generic post-translational modifications from tandem mass spectrometry data

Bioinformatics ◽

10.1093/bioinformatics/btu788 ◽

2014 ◽

Vol 31 (7) ◽

pp. 1141-1143 ◽

Cited By ~ 16

Author(s):

Damian Fermin ◽

Dmitry Avtonomov ◽

Hyungwon Choi ◽

Alexey I. Nesvizhskii

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Mass Spectrometry Data ◽

Tandem Mass ◽

Post Translational Modifications ◽

Site Localization ◽

Tandem Mass Spectrometry Data

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Accelerating the field of epigenetic histone modification through mass spectrometry-based approaches

Molecular & Cellular Proteomics ◽

10.1074/mcp.r120.002257 ◽

2020 ◽

pp. mcp.R120.002257

Author(s):

Congcong Lu ◽

Mariel Coradin ◽

Elizabeth G Porter ◽

Benjamin A Garcia

Keyword(s):

Mass Spectrometry ◽

Molecular Biology ◽

Histone Modification ◽

High Throughput ◽

Epigenetic Regulation ◽

Associated Factors ◽

Chemical Biology ◽

Post Translational Modifications ◽

Histone Ptms ◽

Chromatin Biology

Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Due to its high-throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology and biophysics, MS has been employed to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology.

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