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.
Keywords: mass spectrometry, histone, histone code, post-translational modification, proteomics, chromatin, histone variants, deuterium exchange
Citation: Karch KR, DeNizio JE, Black BE and Garcia BA (2013) Identification and interrogation of combinatorial histone modifications. Front. Genet. 4:264. doi: 10.3389/fgene.2013.00264
Received: 25 September 2013; Paper pending published: 20 October 2013;
Accepted: 15 November 2013; Published online: 20 December 2013.
Edited by:Huabing Li, Yale University School of Medicine, USA
Reviewed by:Steven G. Gray, St James Hospital; Trinity College Dublin, Ireland
Copyright © 2013 Karch, DeNizio, Black and Garcia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Benjamin A. Garcia, Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 1009C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA e-mail: firstname.lastname@example.org