Mechanisms of transcriptional repression by MYC. (a) Antiactivation. In this scenario, MYC represses transcription by blocking the activating functions of another transcription factor; in this case MIZ-1. Association of MYC with MIZ-1 leads to its recruitment to MIZ-1 responsive genes, blocks interaction of MIZ-1 with the p300 histone acetyltransferase, and brings in the DNA methyltransferase Dnmt3a. The effect is to deacetylate histones at the gene (Ac) and cause promoter DNA methylation (Me), thereby shutting down transcription. (b) Repression by HDAC recruitment. In this scenario, MYC recruits HDACs to a set of its target genes, directly leading to histone deacetylation and compaction of chromatin structure to inhibit gene activation. Note that the two scenarios may not be independent (i.e., it may be that HDACs are recruited to MIZ-1 target genes in the presence of MYC).