Detailed Information on Publication Record
2021
Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms-macroH2A1.1 and macroH2A1.2
GIALLONGO, Sebastiano, Oriana LO RE, Gabriela LOCHMANOVÁ, Luca PARCA, Francesco PETRIZZELLI et. al.Basic information
Original name
Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms-macroH2A1.1 and macroH2A1.2
Authors
GIALLONGO, Sebastiano (380 Italy, belonging to the institution), Oriana LO RE (203 Czech Republic), Gabriela LOCHMANOVÁ (203 Czech Republic, belonging to the institution), Luca PARCA (380 Italy), Francesco PETRIZZELLI (380 Italy), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Tommaso MAZZA (380 Italy) and Vinciguerra MANLIO (203 Czech Republic)
Edition
Biology, Basel, MDPI, 2021, 2079-7737
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30500 3.5 Other medical sciences
Country of publisher
Switzerland
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 5.168
RIV identification code
RIV/00216224:14110/21:00119597
Organization unit
Faculty of Medicine
UT WoS
000675987800001
Keywords in English
mass spectrometry; post-translational modifications
Tags
International impact, Reviewed
Změněno: 10/10/2024 14:44, Ing. Martina Blahová
Abstract
V originále
Simple Summary MacroH2A1, a histone H2A variant, is present as two alternative splicing isoforms, macroH2A1.1 and macroH2A1.2, which are finely regulated through several mechanisms, including post-translational modifications (PTM). In this article, the authors provide the PTM pattern of macroH2A1.1 and macroH2A1.2 in the same experimental setting through mass spec analysis. They report a different phosphorylation level in their intrinsically disordered linker region, which can be responsible for their different biological role, as computational analysis shows. Background: Gene expression in eukaryotic cells can be governed by histone variants, which replace replication-coupled histones, conferring unique chromatin properties. MacroH2A1 is a histone H2A variant containing a domain highly similar to H2A and a large non-histone (macro) domain. MacroH2A1, in turn, is present in two alternatively exon-spliced isoforms: macroH2A1.1 and macroH2A1.2, which regulate cell plasticity and proliferation in a remarkably distinct manner. The N-terminal and the C-terminal tails of H2A histones stem from the nucleosome core structure and can be target sites for several post-translational modifications (PTMs). MacroH2A1.1 and macroH2A1.2 isoforms differ only in a few amino acids and their ability to bind NAD-derived metabolites, a property allegedly conferring their different functions in vivo. Some of the modifications on the macroH2A1 variant have been identified, such as phosphorylation (T129, S138) and methylation (K18, K123, K239). However, no study to our knowledge has analyzed extensively, and in parallel, the PTM pattern of macroH2A1.1 and macroH2A1.2 in the same experimental setting, which could facilitate the understanding of their distinct biological functions in health and disease. Methods: We used a mass spectrometry-based approach to identify the sites for phosphorylation, acetylation, and methylation in green fluorescent protein (GFP)-tagged macroH2A1.1 and macroH2A1.2 expressed in human hepatoma cells. The impact of selected PTMs on macroH2A1.1 and macroH2A1.2 structure and function are demonstrated using computational analyses. Results: We identified K7 as a new acetylation site in both macroH2A1 isoforms. Quantitative comparison of histone marks between the two isoforms revealed significant differences in the levels of phosphorylated T129 and S170. Our computational analysis provided evidence that the phosphorylation status in the intrinsically disordered linker region in macroH2A1 isoforms might represent a key regulatory element contributing to their distinct biological responses. Conclusions: Taken together, our results report different PTMs on the two macroH2A1 splicing isoforms as responsible for their distinct features and distribution in the cell.
Links
GF19-29701L, research and development project |
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LM2018127, research and development project |
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MUNI/A/1325/2020, interní kód MU |
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90127, large research infrastructures |
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