DNMT1 [The Human Chemical-Genetic Interaction Map Project]

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======= DNMT1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: DNMT1
  * **<color #00a2e8>Official Name</color>**: DNA methyltransferase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1786|1786]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P26358|P26358]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=DNMT1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DNMT1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/126375|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306). {ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18754681, ECO:0000269|PubMed:24623306}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|DNMT1-RFD|
|BAH|
|DNA methylase|
|DMAP binding|
|zf-CXXC|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|DNA methylation on cytosine within a CG sequence|
|negative regulation of vascular associated smooth muscle cell apoptotic process|
|negative regulation of vascular smooth muscle cell differentiation involved in phenotypic switching|
|negative regulation of cell differentiation involved in phenotypic switching|
|negative regulation of phenotypic switching|
|regulation of vascular smooth muscle cell differentiation involved in phenotypic switching|
|regulation of cell differentiation involved in phenotypic switching|
|DNA (cytosine-5-)-methyltransferase activity|
|C-5 methylation of cytosine|
|DNA-methyltransferase activity|
|DNA methylation on cytosine|
|maintenance of DNA methylation|
|negative regulation of smooth muscle cell apoptotic process|
|regulation of phenotypic switching|
|negative regulation of vascular smooth muscle cell differentiation|
|changes to DNA methylation involved in embryo development|
|DNA methylation involved in embryo development|
|regulation of vascular associated smooth muscle cell apoptotic process|
|positive regulation of methylation-dependent chromatin silencing|
|negative regulation of histone H3-K9 methylation|
|regulation of methylation-dependent chromatin silencing|
|regulation of vascular smooth muscle cell differentiation|
|positive regulation of chromatin silencing|
|pericentric heterochromatin|
|positive regulation of histone H3-K4 methylation|
|negative regulation of smooth muscle cell differentiation|
|negative regulation of histone methylation|
|regulation of histone H3-K9 methylation|
|regulation of smooth muscle cell apoptotic process|
|replication fork|
|methyl-CpG binding|
|regulation of histone H3-K4 methylation|
|regulation of smooth muscle cell differentiation|
|positive regulation of vascular smooth muscle cell proliferation|
|negative regulation of muscle cell apoptotic process|
|regulation of chromatin silencing|
|positive regulation of histone methylation|
|negative regulation of histone modification|
|DNA alkylation|
|DNA methylation|
|promoter-specific chromatin binding|
|regulation of vascular smooth muscle cell proliferation|
|negative regulation of muscle cell differentiation|
|negative regulation of chromatin organization|
|regulation of histone methylation|
|DNA methylation or demethylation|
|regulation of muscle cell apoptotic process|
|cellular response to amino acid stimulus|
|negative regulation of gene expression, epigenetic|
|positive regulation of smooth muscle cell proliferation|
|DNA modification|
|positive regulation of histone modification|
|positive regulation of chromatin organization|
|response to amino acid|
|negative regulation of vasculature development|
|regulation of gene silencing|
|regulation of smooth muscle cell proliferation|
|negative regulation of chromosome organization|
|regulation of histone modification|
|gene silencing|
|regulation of muscle cell differentiation|
|positive regulation of chromosome organization|
|regulation of chromatin organization|
|cellular response to acid chemical|
|regulation of gene expression, epigenetic|
|Ras protein signal transduction|
|macromolecule methylation|
|methylation|
|small GTPase mediated signal transduction|
|regulation of vasculature development|
|response to acid chemical|
|regulation of chromosome organization|
|negative regulation of organelle organization|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|positive regulation of organelle organization|
|cellular response to nitrogen compound|
|chromatin organization|
|negative regulation of cellular component organization|
|negative regulation of cell differentiation|
|DNA metabolic process|
|zinc ion binding|
|negative regulation of transcription by RNA polymerase II|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|positive regulation of cell population proliferation|
|negative regulation of developmental process|
|embryo development|
|negative regulation of cell death|
|response to organonitrogen compound|
|negative regulation of cellular protein metabolic process|
|cellular response to oxygen-containing compound|
|chromosome organization|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|regulation of cell differentiation|
|regulation of protein modification process|
|positive regulation of gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp8|Brefeldin A 0.02μM R00 exp8]]|-1.76|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 3/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 104
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.1 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='DNMT1 Expression in NALM6 Cells: 9.1'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>