LIG_Sin3_2

Gene-specific targeting of the Sin3 co-repressor 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 simultaneously. Sin3 specifically interacts with a diverse set of transcriptional repressors, the first of which were identified as the MAD-family members. Sin3 contains paired amphipatic helix repeat domains (PAH) that mediate 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 protein has two splice isoforms: mSin3A and mSinB. Both have the PAH2 domain and can interact with a SID-containing protein. The structure of the PAH2:MAD1 interaction has been solved (1G1E) (Brubaker,2000). The SID helix is an amphiphatic alpha helix that engages in substantial hydrophobic interactions 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 ultimately leads to deacetylation and repression of transcription.