AUTHOR=Zelenka Tomas , Papamatheakis Dionysios-Alexandros , Tzerpos Petros , Panagopoulos Giorgos , Tsolis Konstantinos C. , Papadakis Vassilis M. , Mariatos Metaxas Dimitris , Papadogkonas George , Mores Eleftherios , Kapsetaki Manouela , Papamatheakis Joseph , Stanek David , Spilianakis Charalampos TITLE=A novel SATB1 protein isoform with different biophysical properties JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=11 YEAR=2023 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1242481 DOI=10.3389/fcell.2023.1242481 ISSN=2296-634X ABSTRACT=

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.