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Tryptase-catalyzed ...
Tryptase-catalyzed core histone truncation : A novel epigenetic regulatory mechanism in mast cells
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- Melo, Fabio R. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Wallerman, Ola (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Paivandy, Aida (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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- Calounova, Gabriela (author)
- Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
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- Gustafson, Ann-Marie (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Sabari, Benjamin R. (author)
- Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA.
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- Zabucchi, Giuliano (author)
- Univ Trieste, Dept Life Sci, Trieste, Italy.
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- Allis, C. David (author)
- Rockefeller Univ, Lab Chromatin Biol & Epigenet, 1230 York Ave, New York, NY 10021 USA.
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- Pejler, Gunnar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University
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- Rosén, Gabriela (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB)
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(creator_code:org_t)
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- MOSBY-ELSEVIER, 2017
- 2017
- English.
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 140:2, s. 474-485
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Keyword
- Mast cells
- epigenetics
- core histones
- histone acetylation
- tryptase
- mMCP6
- secretory granules
- serglycin
- serglycin proteoglycan
- H2B
- H2BK5ac
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Melo, Fabio R.
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Wallerman, Ola
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Paivandy, Aida
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Calounova, Gabri ...
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Gustafson, Ann-M ...
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Sabari, Benjamin ...
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show more...
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Zabucchi, Giulia ...
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Allis, C. David
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Pejler, Gunnar
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Rosén, Gabriela
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
- Articles in the publication
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Journal of Aller ...
- By the university
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Uppsala University
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Swedish University of Agricultural Sciences