CENP-C is a component of the centromere assembly complex in eukaryotes. CENP-C recruits the DNA methyltransferases DNMT3B, in order to establish the necessary epigenetic DNA-methylation essential for maintenance of chromatin structure and genomic stability. This entry represents the middle DNMT3B binding region of CENP-C. Binding of CENP-C and DNMT3B to DNA occurs at both centromeric and peri-centromeric satellite repeats. CENP-C and DNMT3B regulate the histone code in these regions [, , ].
This entry represents protein MENT (methylated in normal thymocytes protein), which is involved in control of cellular proliferation. It is an onconcogenic modifier contributing to the tumour suppressor function of DNMT3B (DNA methyltransferase 3B) []. This entry also includes the mouse Pmis1 protein that may regulate sperm transport into the oviducts and function in modulating sperm-zona binding [].
In mammals, DNA methylation patterns are thought to be established during embryonic development by de novo DNA methyltransferases 3A and 3B (DNMT3A/3B) []. DNMT3A/3B work synergistically to propagate methylation patterns with DNMT3B stimulating DNMT3A activity by promoting its association with nucleosomes []. DNMT3A exists in an autoinhibitory form that can be activated by the histone H3 tail in a DNMT3L-independent manner []. DNMT3A has been linked to cancers [, , ].
This entry represents the ADD domain of DNMT3B. The ADD domain is composed of three clearly distinguishable modules that packtogether through extensive hydrophobic interactions to form a single globulardomain. Packed against this GATA-like finger is a second subdomain,which binds two zinc ions and closely resembles the structure reported forseveral PHD fingers. Finally, there is a long C-terminal α-helix that runsout from the PHD finger and makes extensive hydrophobic contacts with the N-terminal GATA finger, bringing the N- and C-termini of the ADD domain closetogether. This combination of fused GATA-like and PHD fingers within a singledomain is thus far unique [, ].In mammals, DNA methylation patterns are thought to be established during embryonic development by de novo DNA methyltransferases 3A and 3B (DNMT3A/3B) []. DNMT3A/3B work synergistically to propagate methylation patterns with DNMT3B stimulating DNMT3A activity by promoting its association with nucleosomes []. Many DNMT3B isoforms from alternative splicing have been described, among which DNMT3B3 stimulates the basal activity of DNMT3 enzymes, but partially inhibits the stimulatory effect of DNMT3L, whereas DNMT3B4 significantly impairs de novo methylation [, ]. DNMT3B is involved in development and is associated with several diseases, including cancers [].
In mammals, DNA methylation patterns are thought to be established during embryonic development by de novo DNA methyltransferases 3A and 3B (DNMT3A/3B) []. DNMT3A/3B work synergistically to propagate methylation patterns with DNMT3B stimulating DNMT3A activity by promoting its association with nucleosomes []. DNMT3A exists in an autoinhibitory form that can be activated by the histone H3 tail in a DNMT3L-independent manner []. DNMT3A has been linked to cancers [, , ].This entry represents the ADDz domain found in DNA (cytosine-5)-methyltransferase 3A (DNMT3A). The ADD domain is composed of three clearly distinguishable modules that pack together through extensive hydrophobic interactions to form a single globular domain. Packed against this GATA-like finger is a second subdomain, which binds two zinc ions and closely resembles the structure reported for several PHD fingers. Finally, there is a long C-terminal α-helix that runs out from the PHD finger and makes extensive hydrophobic contacts with the N-terminal GATA finger, bringing the N- and C-termini of the ADD domain close together. This combination of fused GATA-like and PHD fingers within a single domain is thus far unique [, ].The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development [, ].
This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domain is composed of three clearly distinguishable modules that packtogether through extensive hydrophobic interactions to form a single globulardomain. Packed against this GATA-like finger is a second subdomain,which binds two zinc ions and closely resembles the structure reported forseveral PHD fingers. Finally, there is a long C-terminal α-helix that runsout from the PHD finger and makes extensive hydrophobic contacts with the N-terminal GATA finger, bringing the N- and C-termini of the ADD domain closetogether. This combination of fused GATA-like and PHD fingers within a singledomain is thus far unique [, ].The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development [, ].
