Article

Revealing histone variant induced changes via quantitative proteomics.

Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Critical Reviews in Biochemistry and Molecular Biology (Impact Factor: 5.81). 04/2011; 46(4):284-94. DOI: 10.3109/10409238.2011.577052
Source: PubMed

ABSTRACT Histone variants are isoforms of linker and core histone proteins that differ in their amino acid sequences. These variants have distinct genomic locations and posttranslational modifications, thus increasing the complexity of the chromatin architecture. Biological studies of histone variants indicate that they play a role in many processes including transcription, DNA damage response, and the cell cycle. The small differences in amino acid sequence and the diverse posttranslational modification states that exist between histone variants make traditional analysis using immunoassay methods challenging. In recent years, a number of mass spectrometric techniques have been developed to identify and quantify histones at the whole protein or peptide levels. In this review, we discuss the biology of histone variants and methods to characterize them using mass spectrometry-based proteomics.

Download full-text

Full-text

Available from: Rosalynn Molden, Jan 15, 2015
0 Followers
 · 
99 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this review is to introduce the exciting field of epigenetics and to describe how it could explain the mechanisms by which environmental changes induce pathological gene expression and determine cell phenotype and function in IBD. We outline how epigenetics research in the context of a variety of clinical conditions, but mainly in cancer, has begun to define the role of multiple combinations of modifications to chromatin, diverse families of enzymes, and non-coding RNAs in determining transcriptional outcomes. These findings are applicable to understanding the context-specific events that underlie the expression of genes in diseases like IBD and have the potential to reveal new targets for improved IBD therapy. The current status of epigenetics-based therapies is also summarized. (Inflamm Bowel Dis 2012).
    Inflammatory Bowel Diseases 01/2012; 18(10):1982-96. DOI:10.1002/ibd.22934 · 5.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the central nervous system, epigenetic processes are involved in a multitude of brain functions ranging from the development and differentiation of the nervous system through to higher-order cognitive processes such as learning and memory. This review summarises the current state of the art for the proteomic analysis of the epigenetic regulation of gene expression, in particular the PTM of histones, in the brain and cellular model systems. It describes the MS technologies that have helped the identification and analysis of histones, histone variants and PTMs in the brain. Strategies for the isolation of histones that allow the qualitative analysis of PTMs and their combinatorial patterns are introduced, methods for the relative and absolute quantification of histone PTMs are described, and future challenges are discussed.
    PROTEOMICS 01/2012; 12:2404-20. · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Histone proteins contribute to the maintenance and regulation of the dynamic chromatin structure, to gene activation, DNA repair and many other processes in the cell nucleus. Site-specific reversible and irreversible post-translational modifications of histone proteins mediate biological functions, including recruitment of transcription factors to specific DNA regions, assembly of epigenetic reader/writer/eraser complexes onto DNA, and modulation of DNA-protein interactions. Histones thereby regulate chromatin structure and function, propagate inheritance and provide memory functions in the cell. Dysfunctional chromatin structures and misregulation may lead to pathogenic states, including diabetes and cancer, and the mapping and quantification of multivalent post-translational modifications has therefore attracted significant interest. Mass spectrometry has quickly been accepted as a versatile tool to achieve insights into chromatin biology and epigenetics. High sensitivity and high mass accuracy and the ability to sequence post-translationally modified peptides and perform large-scale analyses make this technique very well suited for histone protein characterization. In this review we discuss a range of analytical methods and various mass spectrometry-based approaches for histone analysis, from sample preparation to data interpretation. Mass spectrometry-based proteomics is already an integrated and indispensable tool in modern chromatin biology, providing insights into the mechanisms and dynamics of nuclear and epigenetic processes. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry.
    Journal of proteomics 01/2012; 75(12):3419-33. DOI:10.1016/j.jprot.2011.12.029 · 3.93 Impact Factor