title: In situ detection of histone variants and modifications in mouse brain using imaging mass spectrometry.
abstract: Histone posttranslational modifications and histone variants control the epigenetic regulation of gene expression and affect a wide variety of biological processes. A complex pattern of such modifications and variants defines the identity of cells within complex organ systems and can therefore be used to characterize cells at a molecular level. However, their detection and identification in situ has been limited so far due to lack of specificity, selectivity, and availability of antihistone antibodies. Here, we describe a novel MALDI imaging MS based workflow, which enables us to detect and characterize histones by their intact mass and their correlation with cytological properties of the tissue using novel statistical and image analysis tools. The workflow allows us to characterize the in situ distribution of the major histone variants and their modification in the mouse brain. This new analysis tool is particularly useful for the investigation of expression patterns of the linker histone H1 variants for which suitable antibodies are so far not available.
authors.affiliation: Protein Analysis Unit (ZfP), Biomedical Center (BMC), Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
authors.forename: Shibojyoti
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Gene Center, Ludwig Maximilians University, Munich, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Solis-Mezarino
authors.affiliation: Protein Analysis Unit (ZfP), Biomedical Center (BMC), Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fedisch
authors.affiliation: Institute of Stem Cell Research, GSF-National Research Center for Environment and Health, Neuherberg, Germany.|Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilians University of Munich, Munich, Germany.|Institute of Physiological Genomics, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Jovica
authors.initials: J
authors.lastname: Ninkovic
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.affiliation: Institute of Stem Cell Research, GSF-National Research Center for Environment and Health, Neuherberg, Germany.|Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilians University of Munich, Munich, Germany.|Institute of Physiological Genomics, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Protein Analysis Unit (ZfP), Biomedical Center (BMC), Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
mesh_terms: D000107:Acetylation; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D001923:Brain Chemistry; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D057054:Molecular Imaging / Q000379:methods; D010766:Phosphorylation; D025341:Principal Component Analysis; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D049490:Systems Biology / Q000295:instrumentation / Q000379:methods
chemical_list: D002843:Chromatin; D006657:Histones
keywords: Hierarchical clustering analysis; Histone modifications; MALDI imaging mass spectrometry; Nuclear density; Principal component analysis; Systems biology