DNMT3B encodes a DNA methyltransferase prominently involved in de novo DNAm that establishes patterns early in development; it may also contribute to maintenance DNAm.49 Although initially reported for maintaining DNAm at imprinted loci,50 later evidence showed that other members of the DNMT family (DNMT3A and DNMT3L) are required for imprinting, while DNMT3B may not play an essential role.51 Mouse models have shown that complete loss of DNMT3B function is embryonically lethal.50 However, recessive inheritance of rare mutations that render DNMT3B partially functional are known to cause Immunodeficiency, Centromeric instability and Facial dysmorphism (ICF) syndrome, which manifests with growth and neurodevelopmental abnormalities.49 Because of the critical role that DNMT3B plays in establishing methylation, altered expression has been associated with ICF syndrome at >700 genes involved in brain development and other processes.52 These and other genes that are regulated by DNMT3B methylation represent candidate genes that may directly contribute to nicotine dependence susceptibility.
