A novel SATB1 protein isoform with different biophysical properties

Intra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that SATB1 is involved in the regulation of transcription and splicing, both of which displayed deregulation in Satb1 knockout murine thymocytes. More importantly, we character...

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Main Authors: Tomas Zelenka, Dionysios-Alexandros Papamatheakis, Petros Tzerpos, Giorgos Panagopoulos, Konstantinos C. Tsolis, Vassilis M. Papadakis, Dimitris Mariatos Metaxas, George Papadogkonas, Eleftherios Mores, Manouela Kapsetaki, Joseph Papamatheakis, David Stanek, Charalampos Spilianakis
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1242481/full
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author Tomas Zelenka
Tomas Zelenka
Dionysios-Alexandros Papamatheakis
Dionysios-Alexandros Papamatheakis
Petros Tzerpos
Giorgos Panagopoulos
Konstantinos C. Tsolis
Vassilis M. Papadakis
Dimitris Mariatos Metaxas
George Papadogkonas
George Papadogkonas
Eleftherios Mores
Manouela Kapsetaki
Joseph Papamatheakis
Joseph Papamatheakis
David Stanek
Charalampos Spilianakis
Charalampos Spilianakis
author_facet Tomas Zelenka
Tomas Zelenka
Dionysios-Alexandros Papamatheakis
Dionysios-Alexandros Papamatheakis
Petros Tzerpos
Giorgos Panagopoulos
Konstantinos C. Tsolis
Vassilis M. Papadakis
Dimitris Mariatos Metaxas
George Papadogkonas
George Papadogkonas
Eleftherios Mores
Manouela Kapsetaki
Joseph Papamatheakis
Joseph Papamatheakis
David Stanek
Charalampos Spilianakis
Charalampos Spilianakis
author_sort Tomas Zelenka
collection DOAJ
description Intra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that SATB1 is involved in the regulation of transcription and splicing, both of which displayed deregulation in Satb1 knockout murine thymocytes. More importantly, we characterized a novel SATB1 protein isoform and described its distinct biophysical behavior, implicating potential functional differences compared to the commonly studied isoform. SATB1 utilized its prion-like domains to transition through liquid-like states to aggregated structures. This behavior was dependent on protein concentration as well as phosphorylation and interaction with nuclear RNA. Notably, the long SATB1 isoform was more prone to aggregate following phase separation. Thus, the tight regulation of SATB1 isoforms expression levels alongside with protein post-translational modifications, are imperative for SATB1’s mode of action in T cell development. Our data indicate that deregulation of these processes may also be linked to disorders such as cancer.
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spelling doaj.art-e7ff039f651e459dafd05d08f18d20a62023-08-12T00:28:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-08-011110.3389/fcell.2023.12424811242481A novel SATB1 protein isoform with different biophysical propertiesTomas Zelenka0Tomas Zelenka1Dionysios-Alexandros Papamatheakis2Dionysios-Alexandros Papamatheakis3Petros Tzerpos4Giorgos Panagopoulos5Konstantinos C. Tsolis6Vassilis M. Papadakis7Dimitris Mariatos Metaxas8George Papadogkonas9George Papadogkonas10Eleftherios Mores11Manouela Kapsetaki12Joseph Papamatheakis13Joseph Papamatheakis14David Stanek15Charalampos Spilianakis16Charalampos Spilianakis17Department of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceBiomedical Research Foundation, Academy of Athens, Athens, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceDepartment of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceInstitute of Molecular Genetics of the Czech Academy of Sciences, Prague, CzechiaDepartment of Biology, University of Crete, Heraklion, Crete, GreeceInstitute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas, Heraklion, Crete, GreeceIntra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that SATB1 is involved in the regulation of transcription and splicing, both of which displayed deregulation in Satb1 knockout murine thymocytes. More importantly, we characterized a novel SATB1 protein isoform and described its distinct biophysical behavior, implicating potential functional differences compared to the commonly studied isoform. SATB1 utilized its prion-like domains to transition through liquid-like states to aggregated structures. This behavior was dependent on protein concentration as well as phosphorylation and interaction with nuclear RNA. Notably, the long SATB1 isoform was more prone to aggregate following phase separation. Thus, the tight regulation of SATB1 isoforms expression levels alongside with protein post-translational modifications, are imperative for SATB1’s mode of action in T cell development. Our data indicate that deregulation of these processes may also be linked to disorders such as cancer.https://www.frontiersin.org/articles/10.3389/fcell.2023.1242481/fullSATB1T cellschromatin organizationprionphase separation
spellingShingle Tomas Zelenka
Tomas Zelenka
Dionysios-Alexandros Papamatheakis
Dionysios-Alexandros Papamatheakis
Petros Tzerpos
Giorgos Panagopoulos
Konstantinos C. Tsolis
Vassilis M. Papadakis
Dimitris Mariatos Metaxas
George Papadogkonas
George Papadogkonas
Eleftherios Mores
Manouela Kapsetaki
Joseph Papamatheakis
Joseph Papamatheakis
David Stanek
Charalampos Spilianakis
Charalampos Spilianakis
A novel SATB1 protein isoform with different biophysical properties
Frontiers in Cell and Developmental Biology
SATB1
T cells
chromatin organization
prion
phase separation
title A novel SATB1 protein isoform with different biophysical properties
title_full A novel SATB1 protein isoform with different biophysical properties
title_fullStr A novel SATB1 protein isoform with different biophysical properties
title_full_unstemmed A novel SATB1 protein isoform with different biophysical properties
title_short A novel SATB1 protein isoform with different biophysical properties
title_sort novel satb1 protein isoform with different biophysical properties
topic SATB1
T cells
chromatin organization
prion
phase separation
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1242481/full
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