title: Identification and interrogation of combinatorial histone modifications.
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.
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Karch
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Denizio
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
keywords: chromatin; deuterium exchange; histone; histone code; histone variants; mass spectrometry; post-translational modification; proteomics