DNMT3B

DNMT3B

DNMT3B, or DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that plays a crucial role in the epigenetic regulation of gene expression through the process of DNA methylation. This enzyme is part of the DNA methyltransferase family, which is responsible for adding methyl groups to the cytosine residues of CpG dinucleotides in DNA. DNMT3B is particularly important during embryonic development and in the establishment of genomic imprinting.

Function

DNMT3B is primarily involved in de novo methylation, which is the addition of methyl groups to previously unmethylated DNA. This process is essential for the establishment of new methylation patterns during development and for the maintenance of these patterns in somatic cells. DNMT3B works in conjunction with DNMT3A, another de novo methyltransferase, to establish methylation marks that are crucial for normal development and cellular differentiation.

Structure

DNMT3B is a large protein that contains several functional domains:

• PWWP domain: This domain is involved in the recognition of specific DNA sequences and is important for the localization of DNMT3B to chromatin.
• ADD domain: The ADD (ATRX-DNMT3-DNMT3L) domain is involved in the interaction with histone modifications, which can influence the activity of DNMT3B.
• Catalytic domain: This domain is responsible for the transfer of methyl groups from S-adenosylmethionine (SAM) to cytosine residues in DNA.

Clinical Significance

Mutations in the DNMT3B gene have been associated with several human diseases, including Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome. ICF syndrome is a rare autosomal recessive disorder characterized by immunodeficiency, facial anomalies, and centromeric instability of chromosomes 1, 9, and 16. Patients with ICF syndrome often have mutations in the DNMT3B gene that lead to reduced or altered enzyme activity.

DNMT3B is also implicated in cancer. Aberrant methylation patterns, often involving hypermethylation of tumor suppressor genes, are a hallmark of many cancers. Overexpression or mutations of DNMT3B can contribute to the development and progression of cancer by altering the normal methylation landscape of the genome.

Research and Therapeutic Implications

Understanding the role of DNMT3B in epigenetic regulation has significant implications for the development of therapeutic strategies. Inhibitors of DNA methyltransferases, such as 5-azacytidine and decitabine, are used in the treatment of certain cancers, including myelodysplastic syndromes and acute myeloid leukemia. These drugs work by inhibiting the activity of DNMT enzymes, leading to the reactivation of silenced tumor suppressor genes.

Also see

• DNA methylation
• Epigenetics
• DNMT1
• DNMT3A
• Genomic imprinting