A novel SATB1 protein isoform with different biophysical properties

Front Cell Dev Biol. 2023 Aug 11:11:1242481. doi: 10.3389/fcell.2023.1242481. eCollection 2023.


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.

Keywords: SATB1; T cells; chromatin organization; phase separation; prion.

Grants and funding

This work was supported by H2020-MSCA-ETN-2014 (GA642934) (TZ and CS), FONDATION SANTE X-COAT (TZ and CS), Ministry of Education Youth and Sports of the Czech Republic (LM2018129, CZ.02.1.01/0.0/0.0/18_046/0016045) (68378050-KAV-NPUI) (LTAUSA18103) (DS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was supported by the European Union (European Social Fund ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) Research Funding Program ARISTEIA (MIRACLE 42), by FONDATION SANTE (X-COAT) and by Chromatin3D-H2020-MSCA-ITN (GA642934).