DNMT1

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Protein-coding gene in the species Homo sapiens

title: "DNMT1" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/DNMT1" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

DNA (cytosine-5)-methyltransferase 1 (Dnmt1) is an enzyme that catalyzes the transfer of methyl groups to specific CpG sites in DNA, a process called DNA methylation. In humans, it is encoded by the DNMT1 gene. Dnmt1 forms part of the family of DNA methyltransferase enzymes, which consists primarily of DNMT1, DNMT3A, and DNMT3B.

Function

This enzyme is responsible for maintaining DNA methylation, which ensures the fidelity of this epigenetic patterns across cell divisions. In line with this role, it has a strong preference towards methylating CpGs on hemimethylated DNA. However, DNMT1 can catalyze de novo DNA methylation in specific genomic contexts, including transposable elements and paternal imprint control regions. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.

Interactions

DNMT1 has been shown to interact with UHRF1,:

  • DMAP1,
  • DNMT3A
  • DNMT3B,
  • HDAC2,
  • PCNA,
  • RB1. and
  • G9A DNMT1 is highly transcribed during the S phase of the cell cycle when it is required for methylation of the newly generated hemimethylated sites on daughter DNA strands. Its interaction with PCNA and UHRF1 has been implicated in localizing it to the replication fork. The direct co-operation between DNMT1 and G9a coordinates DNA and H3K9 methylation during cell division. This chromatin methylation is necessary for stable repression of gene expression during mammalian development.

Model organisms

Knockout experiments have shown that this enzyme is responsible for the bulk of methylation in mouse cells, and it is essential for embryonic development. It has also been shown that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of imprinted genes in blastocysts.

Clinical significance

DNMT1 plays a critical role in Hematopoietic stem cell (HSC) maintenance. HSCs with reduced DNMT1 fail to self-renew efficiently post-transplantation. It has also been shown to be critical for other stem cell types such as Intestinal stem cells (ISCs) and Mammary stem cells (MaSCs). Conditional deletion of DNMT1 results in overall intestinal hypomethylation, crypt expansion and altered differentiation timing of ISCs, and proliferation and maintenance of MaSCs.

DNMT1 plays a crucial role in maintaining DNA methylation patterns, which are vital for regulating gene expression and maintaining cellular identity in cancer. Dysregulation of DNMT1 can lead to abnormal methylation patterns, contributing to oncogene activation or tumor suppressor gene silencing, thereby promoting cancer progression and metastasis.

Given the role of DNMT1 in maintaining DNA methylation patterns crucial for gene regulation in cancer, the inhibition of DNMT1 by brazilin, a compound from Caesalpinia sappan, is significant. By reducing DNMT1 expression and altering methylation states through activation of p38 MAPK and elevation of p53 in MCF-7 breast cancer cells, brazilin leads to the restoration of p21 expression. This mechanism highlights brazilin's potential as a therapeutic agent to correct epigenetic alterations associated with cancer progression and metastasis.

References

References

  1. (May 1992). "Isolation and characterization of the cDNA encoding human DNA methyltransferase". Nucleic Acids Research.
  2. (November 2004). "The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites". The Journal of Biological Chemistry.
  3. (December 2018). "BAH domains and a histone-like motif in DNA methyltransferase 1 (DNMT1) regulate de novo and maintenance methylation in vivo". The Journal of Biological Chemistry.
  4. (June 2021). "Dnmt1 has de novo activity targeted to transposable elements.". Nature Structural and Molecular Biology.
  5. (June 2011). "Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss". Nature Genetics.
  6. "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1".
  7. (August 2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". The EMBO Journal.
  8. (July 2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Current Biology.
  9. (July 2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nature Genetics.
  10. (October 2002). "PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA". Genes to Cells.
  11. (September 1997). "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1". Science.
  12. (July 2000). "DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters". Nature Genetics.
  13. (November 2006). "Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication". Genes & Development.
  14. (May 2000). "Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells". Nucleic Acids Research.
  15. (November 2009). "Rethinking how DNA methylation patterns are maintained". Nature Reviews. Genetics.
  16. (June 1992). "Targeted mutation of the DNA methyltransferase gene results in embryonic lethality". Cell.
  17. (June 2008). "Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development". Genes & Development.
  18. (October 2009). "DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells". Cell Stem Cell.
  19. (October 2016). "Epigenetic control of adult stem cell function". Nature Reviews. Molecular Cell Biology.
  20. (October 2021). "Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia". Nature Cancer.
  21. (2022-01-01). "The phytochemical brazilin suppress DNMT1 expression by recruiting p53 to its promoter resulting in the epigenetic restoration of p21 in MCF7cells". Phytomedicine.

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