Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms-macroH2A1.1 and macroH2A1.2

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00119597" target="_blank" >RIV/00216224:14110/21:00119597 - isvavai.cz</a>

Alternative codes found

RIV/00159816:_____/21:00075093

Result on the web

<a href="https://www.mdpi.com/2079-7737/10/7/659" target="_blank" >https://www.mdpi.com/2079-7737/10/7/659</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biology10070659" target="_blank" >10.3390/biology10070659</a>

Result language

angličtina

Original language name

Phosphorylation within Intrinsic Disordered Region Discriminates Histone Variant macroH2A1 Splicing Isoforms-macroH2A1.1 and macroH2A1.2

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30500 - Other medical sciences

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biology

ISSN

2079-7737

e-ISSN

2079-7737

Volume of the periodical

10

Issue of the periodical within the volume

7

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

1-13

UT code for WoS article

000675987800001

EID of the result in the Scopus database

2-s2.0-85111159267