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Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells

Mast cells are immune cells that store large amounts of mast cell-restricted proteases in their secretory granules, including tryptase, chymase and carboxypeptidase A3. In mouse mast cells, it has been shown that tryptase, in addition to its canonical location in secretory granules, can be found in...

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Autores principales: Alanazi, Sultan, Rabelo Melo, Fabio, Pejler, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674432/
https://www.ncbi.nlm.nih.gov/pubmed/34925389
http://dx.doi.org/10.3389/fimmu.2021.804408
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author Alanazi, Sultan
Rabelo Melo, Fabio
Pejler, Gunnar
author_facet Alanazi, Sultan
Rabelo Melo, Fabio
Pejler, Gunnar
author_sort Alanazi, Sultan
collection PubMed
description Mast cells are immune cells that store large amounts of mast cell-restricted proteases in their secretory granules, including tryptase, chymase and carboxypeptidase A3. In mouse mast cells, it has been shown that tryptase, in addition to its canonical location in secretory granules, can be found in the nuclear compartment where it can impact on core histones. Here we asked whether tryptase can execute core histone processing in human mast cell leukemia cells, and whether tryptase thereby can affect the epigenetic modification of core histones. Our findings reveal that triggering of cell death in HMC-1 mast cell leukemia cells is associated with extensive cleavage of core histone 3 (H3) and more restricted cleavage of H2B. Tryptase inhibition caused a complete blockade of such processing. Our data also show that HMC-1 cell death was associated with a major reduction of several epigenetic histone marks, including H3 lysine-4-mono-methylation (H3K4me1), H3K9me2, H3 serine-10-phosphorylation (H3S10p) and H2B lysine-16-acetylation (H2BK16ac), and that tryptase inhibition reverses the effect of cell death on these epigenetic marks. Further, we show that tryptase is present in the nucleus of both viable and dying mast cell leukemia cells. In line with a role for tryptase in regulating nuclear events, tryptase inhibition caused increased proliferation of the mast cell leukemia cells. Altogether, the present study emphasizes a novel principle for how epigenetic modification of core histones is regulated, and provides novel insight into the biological function of human mast cell tryptase.
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spelling pubmed-86744322021-12-17 Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells Alanazi, Sultan Rabelo Melo, Fabio Pejler, Gunnar Front Immunol Immunology Mast cells are immune cells that store large amounts of mast cell-restricted proteases in their secretory granules, including tryptase, chymase and carboxypeptidase A3. In mouse mast cells, it has been shown that tryptase, in addition to its canonical location in secretory granules, can be found in the nuclear compartment where it can impact on core histones. Here we asked whether tryptase can execute core histone processing in human mast cell leukemia cells, and whether tryptase thereby can affect the epigenetic modification of core histones. Our findings reveal that triggering of cell death in HMC-1 mast cell leukemia cells is associated with extensive cleavage of core histone 3 (H3) and more restricted cleavage of H2B. Tryptase inhibition caused a complete blockade of such processing. Our data also show that HMC-1 cell death was associated with a major reduction of several epigenetic histone marks, including H3 lysine-4-mono-methylation (H3K4me1), H3K9me2, H3 serine-10-phosphorylation (H3S10p) and H2B lysine-16-acetylation (H2BK16ac), and that tryptase inhibition reverses the effect of cell death on these epigenetic marks. Further, we show that tryptase is present in the nucleus of both viable and dying mast cell leukemia cells. In line with a role for tryptase in regulating nuclear events, tryptase inhibition caused increased proliferation of the mast cell leukemia cells. Altogether, the present study emphasizes a novel principle for how epigenetic modification of core histones is regulated, and provides novel insight into the biological function of human mast cell tryptase. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8674432/ /pubmed/34925389 http://dx.doi.org/10.3389/fimmu.2021.804408 Text en Copyright © 2021 Alanazi, Rabelo Melo and Pejler https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Alanazi, Sultan
Rabelo Melo, Fabio
Pejler, Gunnar
Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title_full Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title_fullStr Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title_full_unstemmed Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title_short Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
title_sort tryptase regulates the epigenetic modification of core histones in mast cell leukemia cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674432/
https://www.ncbi.nlm.nih.gov/pubmed/34925389
http://dx.doi.org/10.3389/fimmu.2021.804408
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