RGD Reference Report - A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation.

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A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation.
Authors:	Chen, T Ueda, Y Xie, S Li, E
Citation:	Chen T, etal., J Biol Chem. 2002 Oct 11;277(41):38746-54. Epub 2002 Jul 22.
RGD ID:	8554662
Pubmed:	PMID:12138111 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M205312200 (Journal Full-text)
Previous studies have shown that the Dnmt3b gene encodes multiple variants via alternative splicing. However, only one form of Dnmt3a has been identified to date. We report here the discovery of a small form of Dnmt3a, denoted Dnmt3a2, from both human and mouse. The transcript encoding Dnmt3a2 is initiated from a downstream intronic promoter. As a result, the Dnmt3a2 protein lacks the N-terminal 223 (human) or 219 (mouse) amino acid residues of the full-length Dnmt3a. Recombinant Dnmt3a2 protein displayed similar cytosine methyltransferase activity as Dnmt3a in vitro. However, Dnmt3a and Dnmt3a2 exhibited strikingly different subcellular localization patterns. Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. Dnmt3a2 is the predominant form in embryonic stem cells and embryonal carcinoma cells and can also be detected from testis, ovary, thymus, and spleen, whereas Dnmt3a is expressed at low levels ubiquitously. Comparison of human embryonal carcinoma cell lines with breast/ovarian cancer cell lines indicates that DNMT3A2 expression correlates with high de novo methylation activity. These findings suggest that Dnmt3a and Dnmt3a2 may have distinct DNA targets and different functions in development.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dnmt3a	Rat	negative regulation of gene expression via chromosomal CpG island methylation	involved_in	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dnmt3a	Rat	cytoplasm	located_in	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt
Dnmt3a	Rat	euchromatin	located_in	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt
Dnmt3a	Rat	nuclear matrix	located_in	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt
Dnmt3a	Rat	nucleus	located_in	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt

Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Dnmt3a	Rat	DNA (cytosine-5-)-methyltransferase activity	enables	ISS	UniProtKB:Q9Y6K1	PMID:12138111	UniProt

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Genes (Rattus norvegicus)

Dnmt3a (DNA methyltransferase 3 alpha)

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A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation.