Background: DNA methylation can help to regulate transcriptional silencing via repressive transcription complexes, which include methyl-CpG-binding domain proteins and histone deacetylases (HDACs) DNMT1, the core enzyme for mammalian DNA methylation, can also establish a repressive transcription complex consisting of DNMT1, HDAC2, and a third protein, termed DMAP1 for 'DNMT1-associated protein.' The 467-amino acid DMAP1 protein shares approximately 98% amino acid sequence homology with the mouse protein. DMAP1 interacts directly with the N-terminal region of DNMT1, and DMAP1 can repress transcription independently of histone deacetylase activity. DNMT1, HDAC2, and DMAP1 form a complex in vivo, and DMAP1 can interact directly with the transcriptional corepressor TSG101. The DNMT1-DMAP1exists throughout the S phase, HDAC2 joins DNMT1 and DMAP1 only during late S phase. This provides a regulated means to deacetylate heterochromatin following replication.