DNA binding discrimination of the murine DNA cytosine-C 5 methyltransferase 1 1Edited by A. Klug

A Potent Cell-active Allosteric Inhibitor of Murine DNA Cytosine C5 Methyltransferase

“…2B, are in good agreement at about 30 nM. In the absence of poly(dI⅐dC), GC-box bMET binds free enzyme with a dissociation constant of 880 nM (21). Therefore, poly(dI⅐dC) stabilizes GC-box bMET binding 29-fold.…”

“…Some single-stranded oligonucleotides are proposed to form transient duplexes that are then acted upon by the enzyme (31); the CRE and GC-box-derived single strands used in our study show no such behavior (41). In contrast to the CRE-derived strands, single-stranded substrates mimicking the GC-box element, showed no detectable activity (41) despite the ability of the enzyme to bind such sequences with good affinity (21). We therefore speculated that the single-stranded GC-box oligonucleotides could act as deadend inhibitors of the enzyme.…”

“…Early evidence indicated that Dnmt1 binds a second DNA molecule at an unidentified allosteric site (20,21) and that N-terminal domain-derived peptides bind nucleic acids (26). These interactions recently have been characterized in detail (22,(27)(28)(29).…”

Profound Flanking Sequence Preference of Dnmt3a and Dnmt3b Mammalian DNA Methyltransferases Shape the Human Epigenome

“…Dnmt1 has been found to have several-fold higher preference for hemimethylated CG when compared to unmethylated substrate. [7][8][9][10] There is no preference for flanking sequences reported for Dnmt1, although highly GC-rich flanking sequences have been found to bind to the enzyme with higher affinity. 8 In mammalian genomes some non-CG cytosine residues have also been found to be methylated.…”

“…The methylation pattern is inherited by daughter cell genomes during DNA replication by the action of DNA methyltransferase 1 (Dnmt1), which exhibits high preference for a hemimethylated DNA substrate. [7][8][9][10] The genomic methylation pattern is set by de novo DNA methylation during gametogenesis in a sexspecific fashion and later, after extensive demethylation of the genome, during embryogenesis. 5,11 The de novo methylation is carried out by two de novo DNA methyltransferases (MTases), Dnmt3a and Dnmt3b, which methylate unmethylated and hemimethylated DNA.…”