Defining the heterochromatin localization and repression domains of SALL1

SALL1 has been identified as one of four human homologues of the Drosophila region-specific homeotic gene spalt (sal), encoding zinc finger proteins of characteristic structure. Mutations of SALL1 on chromosome 16q12.1 cause Townes–Brocks syndrome (TBS, OMIM 107480). We have shown previously that SALL1 acts as a strong transcriptional repressor in mammalian cells when fused to a heterologous DNA-binding domain. Here, we report that SALL1 contains two repression domains, one located at the extreme N-terminus of the protein and the other in the central region. SALL1 fragments with the central repression domain exhibited a punctate nuclear distribution pattern at pericentromeric heterochromatin foci in murine NIH-3T3 cells, suggesting an association between repression and heterochromatin localization. The implications of these findings for the pathogenesis of Townes–Brocks syndrome are discussed.