SIN3 COREPRESSOR FUNCTION IN MYC-INDUCED TRANSCRIPTION AND TRANSFORMATION

Many basic-helix-loop-helix-leucine zipper (b-HLH-LZ) proteins, includ ing the Myc family and non-Myc family, bind a common DNA sequence CACG TG, yet have quite different biological actions. Myc binds this sequen ce as a heterodimer with Max in the activation of both transcription a nd transformation. The Myc family members Mad and Mxi1 are known to su ppress Myc-induced transcription and transformation and to dimerize wi th Max to form ternary complexes with the mammalian Sin3 transcription al corepressor (mSin3). The b-HLH-LZ domain of TFEB, which cannot hete rodimerize within the Myc family, does not suppress Myc-induced transc ription or transformation. However, transfer of a 25- to 36-aa region from Mad or Mxi1, which interacts with mSin3, to the b-HLH-LZ of TFEB, mediated profound suppression of Myc-induced transcription and transf ormation. These results suggest that the DNA binding specificities of the Myc family and non-Myc family b-HLH-LZ proteins, in the context of the cellular genes involved in Myc-induced transformation, are shared . The results also demonstrate that targeting mSin3 to CACGTG sites vi a a non-Myc family DNA binding domain is sufficient to oppose Myc acti vity in growth regulation.