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Tryptase-catalyzed core histone truncation: A novel epigenetic regulatory mechanism in mast cells.

Authors :
Melo FR
Wallerman O
Paivandy A
Calounova G
Gustafson AM
Sabari BR
Zabucchi G
Allis CD
Pejler G
Source :
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2017 Aug; Vol. 140 (2), pp. 474-485. Date of Electronic Publication: 2017 Jan 17.
Publication Year :
2017

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.<br />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.<br />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.<br />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.<br />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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-6825
Volume :
140
Issue :
2
Database :
MEDLINE
Journal :
The Journal of allergy and clinical immunology
Publication Type :
Academic Journal
Accession number :
28108335
Full Text :
https://doi.org/10.1016/j.jaci.2016.11.044