DNMT3B Gene

The DNMT3B gene (DNMT3B stands for "DNA Methyltransferase 3 Beta") is a protein-coding gene located on chromosome 20q11.2. Eight alternatively spliced transcript variants have been described. The full-length sequences of variants 4 and 5 have not been determined.

The encoded protein, a DNA methyltransferase is required for genome-wide de novo methylation and essential for the establishment of DNA methylation patterns during development. The protein is mainly localized in the nucleus, and its expression is regulated by development. DNA methylation is coordinated with histone methylation. Isoforms 4 and 5 are probably non-functional due to deletion of two conserved methyltransferase motifs.

CpG methylation is an epigenetic change that is important for embryonic development, imprinting and inactivation of the X chromosome. Mutations in this gene cause

• ICF syndrome (Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 1) and
• Facioscapulohumeral muscular dystrophy 4

1. Brown DC et al (1995) ICF syndrome (immunodeficiency, centromeric instability and facial anomalies): investigation of heterochromatin abnormalities and review of clinical outcome. Hum. Genet 96: 411-416.
2. Fasth A et al. (1990) Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings: a recessively inherited entity? Acta Paediat Scand 79: 605-612.
3. Haas OA etal. (1990) Centromeric heterochromatin instability of chromosomes 1, 9, and 16 in variable immunodeficiency syndrome--a virus-induced phenomenon? Hum Genet 85: 244-246.
4. Jin B et al. DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Molec Genet 17: 690-709.
5. Tiepolo L et al (1979) Multibranched chromosomes 1, 9 and 16 in a patient with combined IgA and IgE deficiency. Hum Genet 51: 127-137.
6. Valkova G et al (1987) Centromeric instability of chromosomes 1, 9 and 16 with variable immune deficiency: support of a new syndrome. Clin Genet 31: 119-124.