The human SIN3B corepressor forms a nucleolar complex with leukemia-associated ETO homologues

Abstract

Background: SIN3 (SWI-Independent) is part of a transcriptional deacetylase complex, which generally mediates the formation of repressive chromatin. The purpose of this work was to study possible interactions between corepressors human SIN3B (hSIN3B) and the ETO homologues - ETO (eight twenty-one), MTG16 (myeloid-transforming gene 16) and MTGR1 (MTG-related protein 1). In addition, the subnuclear localization of the hSIN3B and the ETO homologues was also examined.

Results: A ubiquitous expression of hSIN3B was observed in adult and fetal tissues. Results with both ectopically expressed proteins in COS-7 cells and endogeneous proteins in the K562 human erytholeukemia cell line demonstrated interactions between hSIN3B and ETO or MTG16 but not MTGR1. Furthermore, nuclear extract of primary placental cells showed complexes between hSIN3B and ETO. The interaction between hSIN3B and ETO required an intact amino-terminus of ETO and the NHR2 domain. A nucleolar localization of hSIN3B and all the ETO homologues was demonstrated upon overexpression in COS-7 cells, and confirmed for the endogeneously expressed proteins in K562 cells. However, hSIN3B did not colocalize or interact with the leukemia-associated AML1 -ETO.

Conclusion: Our data from protein-protein interactions and immunolocalization experiments support that hSIN3B is a potential member of a corepressor complex involving selective ETO homologues.