Search results for DNMT1

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Reaction (3 results from a total of 21)

Identifier: R-HSA-5334151
Species: Homo sapiens
Compartment: nucleoplasm
DNMT1 transfers a methyl group from S-adenosylmethionine to the 5-position of the cytosine ring of cytosine residues in DNA. Purified human DNMT1 shows a 7 to 21-fold preference for hemimethylated CG motifs in DNA compared to unmethylated CG motifs (Pradhan et al. 1999) thus DNMT1 tends to maintain existing methylation through DNA replication. The binding of the CXXC motif of DNMT1 to cytosine in symmetrically unmethylated CG dinucleotides prevents access of cytosine to the active site and thereby prevents de novo methylation (Song et al. 2011). UHRF1 binds hemimethylated DNA and histone H3 tails methylated at lysine-9 and recruits DNMT1 to methylate hemimethylated DNA (Bostick et al. 2007, reviewed in Ooi and Bestor 2008). Interaction of UHRF1 with DNMT1 increases the methylation activity of DNMT1 about 5-fold (Bashtrykov et al. 2014).
Identifier: R-HSA-9851145
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
miR-21 represses the translation of DNMT1 mRNA. In the context of NPM1-ALK signaling, DNMT1 contributes to the repression of IL2RG expression through promoter methylation; STAT3 contributes to this repression in two ways, by directly recruiting DNMT1 to the IL2RG promoter, and by downregulating MIR21 gene expression, allowing DNMT1 levels to increase (Zhang et al, 2011).
Identifier: R-HSA-9851147
Species: Homo sapiens
Compartment: cytosol
Translation of DNMT1 mRNA is negatively regulated by miR-21 (Zhang et al, 2011). In the context of NPM1-ALK signaling in ALCL, DNMT1 represses IL2RG gene expression by methylating the IL2RG promoter. STAT3 contributes to IL2RG repression both by faciliating the recruitment of repressors SIN3A and DNMT1 to the promoter, and by directly repressing miR-21 expression (Zhang et al, 2011; Gambi et al, 2019; reviewed in Fuchs et al, 2019).

Complex (3 results from a total of 7)

Identifier: R-HSA-5334177
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9850883
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-212288
Species: Homo sapiens
Compartment: nucleoplasm
The Polycomb Repressor Complex 2 (PRC2) is able to interact with and recruit DNMT1, DNMT3a, and DNMT3b, all of which transfer a methyl group from S-adenosylmethionine to the 5 position of the cytosine ring.EZH2 is required for DNA methylation at PRC2 targets.

Pathway (3 results from a total of 8)

Identifier: R-HSA-427413
Species: Homo sapiens
Compartment: nucleoplasm
The Nucleolar Remodeling Complex (NoRC) comprising TIP5 (BAZ2A) and the chromatin remodeller SNF2H (SMARCA5) silences rRNA gene (reviewed in Santoro and Grummt 2001, Grummt 2007, Preuss and Pikaard 2007, Birch and Zommerdijk 2008, McStay and Grummt 2008, Grummt and Langst 2013). The TAM domain of TIP5 (BAZ2A) binds promoter-associated RNA (pRNA) transcribed from the intergenic spacer region of rDNA. The pRNA bound by TIP5 is required to direct the complex to the main promoter of the rRNA gene possibly by triple helix formation between pRNA and the rDNA. The PHD domain of TIP5 binds histone H4 acetylated at lysine-16. Transcription Termination Factor-I (TTF-I) binds to a promoter-proximal terminator (T0 site) in the rDNA and interacts with the TIP5 subunit of NoRC. NoRC also interacts with the SIN3-HDAC complex, HDAC1, HDAC2, DNMT1, and DNMT3B. DNMT3B interacts with a triple helix formed by pRNA and the rDNA. HDAC1, DNMT1, and DNMT3B have been shown to be required for proper DNA methylation of silenced rRNA gene copies, although the catalytic activity of DNMT3B was not required.
Identifier: R-HSA-5250941
Species: Homo sapiens
Compartment: nucleoplasm
Transcription of rRNA genes is controlled by epigenetic activation and repression (reviewed in McStay and Grummt 2008, Goodfellow and Zomerdijk 2012, Grummt and Langst 2013). About half of the roughly 400 rRNA genes are expressed and these have the modifications of active chromatin: unmethylated DNA and acetylated histones. Repressed genes generally have methylated DNA and histone H3 methylated at lysine-9. Regulators of repression include the eNoSC complex, SIRT1, and the NoRC complex.
SIRT1 negatively regulates rRNA expression as a subunit of the eNoSC complex, which deacetylates histone H3 and dimethylates lysine-9 of histone H3 (H3K9me2).
NoRC negatively regulates rRNA expression by shifting a nucleosome near the start of rRNA transcription into a more repressive location and recruiting Histone Deacetylase 1 and 2 (HDAC1, HDAC2) and DNA Methyltransferase 1 and 3b (DNMT1, DNMT3b).
Identifier: R-HSA-5334118
Species: Homo sapiens
Compartment: nucleoplasm
Methylation of cytosine is catalyzed by a family of DNA methyltransferases (DNMTs): DNMT1, DNMT3A, and DNMT3B transfer methyl groups from S-adenosylmethionine to cytosine, producing 5-methylcytosine and homocysteine (reviewed in Klose and Bird 2006, Ooi et al. 2009, Jurkowska et al. 2011, Moore et al. 2013). (DNMT2 appears to methylate RNA rather than DNA.) DNMT1, the first enzyme discovered, preferentially methylates hemimethylated CG motifs that are produced by replication (template strand methylated, synthesized strand unmethylated). Thus it maintains existing methylation through cell division. DNMT3A and DNMT3B catalyze de novo methylation at unmethylated sites that include both CG dinucleotides and non-CG motifs.
DNA from adult humans contains about 0.76 to 1.00 mole percent 5-methylcytosine (Ehrlich et al. 1982, reviewed in Klose and Bird 2006, Ooi et al. 2009, Moore et al. 2013). Methylation of DNA occurs at cytosines that are mainly located in CG dinucleotides. CG dinucleotides are unevenly distributed in the genome. Promoter regions tend to have a high CG-content, forming so-called CG-islands (CGIs), while the CG-content in the remaining part of the genome is much lower. CGIs tend to be unmethylated, while the majority of CGs outside CGIs are methylated. Methylation in promoters and first exons tends to repress transcription while methylation in gene bodies (regions of genes downstream of the promoter and first exon) correlates with transcription (reviewed in Ehrlich and Lacey 2013, Kulis et al. 2013). Proteins such as MeCP2 and MBDs specifically bind 5-methylcytosine and may recruit other factors.
Mammalian development has two major episodes of genome-wide demethylation and remethylation (reviewed in Zhou 2012, Guibert and Weber 2013, Hackett and Surani 2013, Dean 2014). In mice about 1 day after fertilization the paternal genome is actively demethylated by TET proteins together with thymine DNA glycosylase and the maternal genome is demethylated by passive dilution during replication, however methylation at imprinted sites is maintained. The genome has its lowest methylation level about 3.5 days post-fertilization. Remethylation occurs by 6.5 days post-fertilization. The second demethylation-remethylation event occurs in primordial germ cells of the developing embryo about 12.5 days post-fertilization. DNMT3A and DNMT3B, together with the non-catalytic DNMT3L, play major roles in the remethylation events (reviewed in Chen and Chan 2014). How the methyltransferases are directed to particular regions of the genome remains an area of active research. The mechanisms at each locus may differ in detail but a connection between histone modifications and DNA methylation has been observed (reviewed in Rose and Klose 2014).
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