This entry represents a domain found in DNA methyltransferase 1-associated protein 1 (DMAP1). DNA methylation can contribute to transcriptional silencing through several transcriptionally repressive complexes, which include methyl-CpG binding domain proteins (MBDs) and histone deacetylases (HDACs). The chief enzyme that maintains mammalian DNA methylation, DNMT1, can also establish a repressive transcription complex. The non-catalytic N terminus of DNMT1 binds to HDAC2 and DMAP1, and can mediate transcriptional repression. DMAP1 has intrinsic transcription repressive activity, and binds to the transcriptional co-repressor TSG101. DMAP1 is targeted to replication foci through interaction with the far N terminus of DNMT1 throughout S phase, whereas HDAC2 joins DNMT1 and DMAP1 only during late S phase, providing a platform for how histones may become deacetylated in heterochromatin following replication [].
This domain is part of a cytosine specific DNA methyltransferase enzyme (DNMT). It functions non-catalytically to target the protein towards replication foci. This allows the DNMT1 protein to methylate the correct residues. This domain targets DMAP1 and HDAC2 to the replication foci during the S phase of mitosis. They are thought to have some importance in conversion of critical histone lysine moieties [].A structure exists for the human cytosine specific DNA methyltransferase replication foci domain [].
This entry represents DNA (cytosine-5)-methyltransferase 1 (Dnmt1; ), which methylates CpG residues, with a preference for hemimethylated DNA. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Dnmt1 mediates transcriptional repression (silencing) by establishing a repressive transcription complex where the N terminus of Dnmt1 binds to HDAC2 (histone deacetylase-2) as well as to DMAP1 (Dnmt1-associated protein) []. LSH, which is related to the SNF2 chromatin-remodelling ATPases, is also required for efficient DNA methylation [].
This is a ~120-amino acid protein-protein interaction module that binds DMAP1 (DNA methyltransferase-associated protein 1), a transcriptional co-repressor. It is found at the N terminus of DNMT1 (DNA methyltransferase 1) []and animal disco-interacting protein 2 (DIP-2), a protein that maintains morphology of mature neurons [, ]. This domain is also found in N-acetylglucosamine-1-phosphotransferase subunits alpha/beta (GNPTA) and gamma (GNPTG) from animals, which are members of a complex that catalyses the initial step in the formation of the mannose 6-phopsphate targeting signal on newly synthesized lysosomal acid hydrolases. The DMAP1-binding domain mediates the selective binding GlcNAc-1-phosphotranferase to acid hydrolases [, ].The DMAP1-binding domain is predicted to adopt a long helix-turn-helix structure that is rich in leucine residues [].
This entry consists of the SWR1-complex protein 4 (Swc4) from yeast, also known as EAF2, and its mammalian homologue DNA methyltransferase 1-associated protein 1 (Dmap1) []. They are components of the NuA4 histone acetyltransferase (HAT) complex, which is highly conserved in eukaryotes. NuA4 acetylates the nucleosomal histones H4 and H2A and plays primary roles in transcription, DNA repair, and cell cycle control [, ].The subunits of the NuA4 complex are shared by the ATP-dependent chromatin-remodeling SWR1 complex in yeast and its human orthologue, Snf 2-related CREB-binding protein (CBP) activator protein (SRCAP) complex. The mammalian NuA4 complex includes the SRCAP complex, and thus combines the functions of the yeast NuA4 and Swr1 complexes []. The SWR1/SRCAP complex mediates the ATP-dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling [, , ]. Dmap1 was originally identified as an interacting molecule with DNA methyltransferase 1 (DNMT1) and plays a crucial role in DNA repair. It is indispensable for the maintenance of chromosomal integrity and might function as a tumor suppressor [].
