Abstract
Histone proteins are dynamically modified to mediate a variety of cellular processes including gene transcription, DNA damage repair, and apoptosis. Regulation of these processes occurs through the recruitment of non-histone proteins to chromatin by specific combinations of histone post-translational modifications (PTMs). Mass spectrometry has emerged as an essential tool to discover and quantify histone PTMs both within and between samples in an unbiased manner. Developments in mass spectrometry that allow for characterization of large histone peptides or intact protein has made it possible to determine which modifications occur simultaneously on a single histone polypeptide. A variety of techniques from biochemistry, biophysics, and chemical biology have been employed to determine the biological relevance of discovered combinatorial codes. This review first describes advancements in the field of mass spectrometry that have facilitated histone PTM analysis and then covers notable approaches to probe the biological relevance of these modifications in their nucleosomal context.
Highlights
Nucleosomes, the basic repeating unit of chromatin, consist of ∼147 bp DNA wound around a histone core containing two copies of the histone proteins H2A, H2B, H3, and H4 (Luger et al, 1997)
Histones undergo dynamic post-translational modifications (PTMs) on specific residues, most of which are contained on the flexible N-terminal tail that protrudes from the nucleosomal surface (Cosgrove, 2007)
FOR PROBING THE BIOLOGICAL RELEVANCE OF IDENTIFIED HISTONE COMBINATORIAL CODES The first half of this review focused on using Mass spectrometry (MS) to confirm, identify, and quantify histone variants and combinatorial PTMs
Summary
Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Histone proteins are dynamically modified to mediate a variety of cellular processes including gene transcription, DNA damage repair, and apoptosis. Regulation of these processes occurs through the recruitment of non-histone proteins to chromatin by specific combinations of histone post-translational modifications (PTMs). A variety of techniques from biochemistry, biophysics, and chemical biology have been employed to determine the biological relevance of discovered combinatorial codes. This review first describes advancements in the field of mass spectrometry that have facilitated histone PTM analysis and covers notable approaches to probe the biological relevance of these modifications in their nucleosomal context
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