Abstract

Gene specific targeting of the Sin3 corepressor complex by DNA-bound repressors is an important mechanism of gene silencing in eukaryotes. The Sin3 co-repressor is a scaffold protein able to interact with several proteins simultaniously. Sin3 specifically interacts with diverse transcriptional repressors, and was first identified as the MAD-family members.

Sin3 contains paired amphipatic helix repeat domains (PAH) which mediates protein-protein interactions, in addition Sin3 has a histone deacetylase binding site. The SID (Sin3 interacting domain), motif specifically interacts with the PAH2 domain in Sin3. In humans the Sin3 proteins has two spleicoforms; mSin3A and mSinB, both has the PAH2 domain and can interact with a SID containing protein.

The structure of the PAH2:MAD1 interaction has been solved (Brubaker et al., 2000). The SID helix is an amphiphatic alpha helix that engages in substancial hydrophobic interaction with a deep hydrophobic groove defined by two PAH2 helices.

Presumably all SID containing proteins are targeted to a DNA region either by direct DNA binding or interaction with a DNA binding partner, and recruit the Sin3-complex, which ultimatly leads to deacetylation and repression of transcription.