title: Tryptase-catalyzed core histone truncation: A novel epigenetic regulatory mechanism in mast cells.
abstract: BACKGROUND
  Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study, we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends.
  
  
  OBJECTIVE
  Considering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells.
  
  
  METHODS
  Mast cells were cultured from wild-type and tryptase null mice, followed by an assessment of their profile of epigenetic histone modifications and their phenotypic characteristics.
  
  
  RESULTS
  We show that tryptase truncates nucleosomal histone 3 and histone 2B (H2B) and that its absence results in accumulation of the epigenetic mark, lysine 5-acetylated H2B. Intriguingly, the accumulation of lysine 5-acetylated H2B was cell age-dependent and was associated with a profound upregulation of markers of non-mast cell lineages, loss of proliferative control, chromatin remodeling as well as extensive morphological alterations.
  
  
  CONCLUSIONS
  These findings introduce tryptase-catalyzed histone clipping as a novel epigenetic regulatory mechanism, which in the mast cell context may be crucial for maintaining cellular identity.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. Electronic address: Fabio.Melo@imbim.uu.se.
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Melo
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Wallerman
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Aida
authors.initials: A
authors.lastname: Paivandy
authors.affiliation: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calounova
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Gustafson
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Sabari
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Zabucchi
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden. Electronic address: Gunnar.Pejler@imbim.uu.se.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D000107:Acetylation; D048729:Anacardic Acids / Q000494:pharmacology; D000818:Animals; D056649:Cathepsin G / Q000235:genetics; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011509:Proteoglycans / Q000235:genetics; D053802:Tryptases / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: D048729:Anacardic Acids; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin; C088115:anacardic acid; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D053802:Tryptases; D008239:Lysine
keywords: H2B; H2BK5ac; Mast cells; core histones; epigenetics; histone acetylation; mMCP6; secretory granules; serglycin; serglycin proteoglycan; tryptase