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:	Sultan Alanazi, Fabio Rabelo Melo, Gunnar Pejler
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tryptase histones mast cells epigenetics apoptosis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/755d12320a4b40128ba34a507fad8bb9
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spelling	oai:doaj.org-article:755d12320a4b40128ba34a507fad8bb92021-12-02T07:04:51ZTryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells1664-322410.3389/fimmu.2021.804408https://doaj.org/article/755d12320a4b40128ba34a507fad8bb92021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.804408/fullhttps://doaj.org/toc/1664-3224Mast 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.Sultan AlanaziFabio Rabelo MeloGunnar PejlerFrontiers Media S.A.articletryptasehistonesmast cellsepigeneticsapoptosisImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tryptase histones mast cells epigenetics apoptosis Immunologic diseases. Allergy RC581-607
spellingShingle	tryptase histones mast cells epigenetics apoptosis Immunologic diseases. Allergy RC581-607 Sultan Alanazi Fabio Rabelo Melo Gunnar Pejler Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells
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.
format	article
author	Sultan Alanazi Fabio Rabelo Melo Gunnar Pejler
author_facet	Sultan Alanazi Fabio Rabelo Melo Gunnar Pejler
author_sort	Sultan Alanazi
title	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_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_sort	tryptase regulates the epigenetic modification of core histones in mast cell leukemia cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/755d12320a4b40128ba34a507fad8bb9
work_keys_str_mv	AT sultanalanazi tryptaseregulatestheepigeneticmodificationofcorehistonesinmastcellleukemiacells AT fabiorabelomelo tryptaseregulatestheepigeneticmodificationofcorehistonesinmastcellleukemiacells AT gunnarpejler tryptaseregulatestheepigeneticmodificationofcorehistonesinmastcellleukemiacells
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Tryptase Regulates the Epigenetic Modification of Core Histones in Mast Cell Leukemia Cells

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