Neutrophil Elastase in the capacity of the “H2A-specific protease”

•The H2A specific protease (H2Asp) clips histone H2A at V114 but was never identified since its discovery over 35 years ago.•We developed an AQUA approach for high throughput quantitation of V114 clipping.•We show that H2Asp actually is Neutrophil Elastase (NE).•NE associates strongly with nucleosom...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2014-06, Vol.51, p.39-44
Main Authors: Dhaenens, M., Glibert, P., Lambrecht, S., Vossaert, L., Van Steendam, K., Elewaut, D., Deforce, D.
Format: Article
Language:English
Subjects:
Animals
Annotations
AQUA
Biochemistry
Biology
Clipping
Elastase
Endopeptidases - metabolism
Fractionation
H2A specific protease
H2AV114
Histone clipping
Histones
Humans
Leukocyte Elastase - metabolism
Mice
Neutrophil Elastase
Protease
Substrate Specificity
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Summary:•The H2A specific protease (H2Asp) clips histone H2A at V114 but was never identified since its discovery over 35 years ago.•We developed an AQUA approach for high throughput quantitation of V114 clipping.•We show that H2Asp actually is Neutrophil Elastase (NE).•NE associates strongly with nucleosomes in differential gradient experiments.•We emphasize the potential implications of H2AV114 clipping in vitro and in vivo. The amino-terminal tail of histones and the carboxy-tail of histone H2A protrude from the nucleosome and can become modified by many different posttranslational modifications (PTM). During a mass spectrometric proteome analysis on haematopoietic cells we encountered a histone PTM that has received only little attention since its discovery over 35 years ago: truncation of the histone H2A C-tail at V114 which is mediated by the “H2A specific protease” (H2Asp). This enzyme is still referenced today but it was never identified. We first developed a sensitive AQUA approach for specific quantitation of the H2AV114 clipping. This clipping was found only in myeloid cells and further cellular fractionation lead to the annotation of the H2Asp as Neutrophil Elastase (NE). Ultimate proof was provided by NE incubation experiments and by studying histone extracts from NE Null mice. The annotation of the H2Asp not only is an indispensable first step in elucidating the potential biological role of this enzymatic interaction but equally provides the necessary background to critically revise earlier reports of H2A clipping.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2014.03.017