DNMT1 : DNA methyltransferase 1

Description

The DNMT1 (DNA methyltransferase 1) is a protein-coding gene located on chromosome 19.

The DNMT1 gene provides instructions for making an enzyme called DNA methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines. DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to move (migrate) and connect with each other, and neuron survival.

DNMT1 methylates CpG residues, preferentially targeting hemimethylated DNA. It associates with DNA replication sites during the S phase, ensuring the methylation pattern is copied to the newly synthesized strand, vital for epigenetic inheritance. DNMT1 also interacts with chromatin during the G2 and M phases, independent of replication, to maintain DNA methylation. It plays a crucial role in preserving methylation patterns established during development, often coordinated with histone methylation. DNMT1 directly binds to HDAC2, mediating transcriptional repression. In conjunction with DNMT3B and the recruitment of CTCFL/BORIS, DNMT1 contributes to the activation of BAG1 gene expression by regulating histone H3 dimethylation at H3K4 and H3K9. It is likely part of a corepressor complex essential for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. DNMT1 is also required to maintain the transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). It associates with promoter regions of tumor suppressor genes (TSGs), contributing to their silencing and promoting tumor growth.

DNMT1 is also known as ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT, m.HsaI.

Associated Diseases

• Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant
• Neuropathy, hereditary sensory, type IE
• Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome
• Charcot-Marie-Tooth disease
• Hereditary sensory and autonomic neuropathy type IE
• Autosomal dominant cerebellar ataxia, deafness, and narcolepsy