Interaction with members of the heterochromatin protein 1 (HP1) family and histone deacetylation are differentially involved in transcriptional silencing by members of the TIF1 family

Mammalian TIF1 alpha and TIF1 beta (KAP-1/KRIP-1) are related transcriptional intermediary factors that possess intrinsic silencing activity. TIF1 alpha is believed to be a euchromatic target for liganded nuclear receptors, while TIF1 beta may serve as a co-repressor for the large family of KRAB domain-containing zinc finger proteins. Here, we report an association of TIF1 beta with both heterochromatin and euchromatin in interphase nuclei. Co-immunoprecipitation of nuclear extracts shows that endogenous TIF1 beta, but not TIF1 alpha, is associated with members of the heterochromatin protein 1 (HPL) family. However, in vitro, both TIF1 alpha and TIF1 beta interact with and phosphorylate the HP1 proteins. This interaction involves a conserved amino acid motif, which is critical for the silencing activity of TIF1 beta but not TIF1 alpha, We further show that trichostatin ii, an inhibitor of histone deacetylases, can interfere with both TIF1 and HP1 silencing. The silencing activity of TIF1 alpha appears to result chiefly from histone deacetylation, whereas that of TIF1 beta may be mediated via both HP1 binding and histone deacetylation.