title: Regulation of SNAIL1 and E-cadherin function by DNMT1 in a DNA methylation-independent context.
abstract: Mammalian DNA methyltransferase 1 (DNMT1) is essential for maintaining DNA methylation patterns after cell division. Disruption of DNMT1 catalytic activity results in whole genome cytosine demethylation of CpG dinucleotides, promoting severe dysfunctions in somatic cells and during embryonic development. While these observations indicate that DNMT1-dependent DNA methylation is required for proper cell function, the possibility that DNMT1 has a role independent of its catalytic activity is a matter of controversy. Here, we provide evidence that DNMT1 can support cell functions that do not require the C-terminal catalytic domain. We report that PCNA and DMAP1 domains in the N-terminal region of DNMT1 are sufficient to modulate E-cadherin expression in the absence of noticeable changes in DNA methylation patterns in the gene promoters involved. Changes in E-cadherin expression are directly associated with regulation of β-catenin-dependent transcription. Present evidence suggests that the DNMT1 acts on E-cadherin expression through its direct interaction with the E-cadherin transcriptional repressor SNAIL1.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Espada
authors.forename: Hector
authors.initials: H
authors.lastname: Peinado
authors.forename: Lidia
authors.initials: L
authors.lastname: Lopez-Serra
authors.forename: Fernando
authors.initials: F
authors.lastname: Setién
authors.forename: Paula
authors.initials: P
authors.lastname: Lopez-Serra
authors.forename: Anna
authors.initials: A
authors.lastname: Portela
authors.forename: Jaime
authors.initials: J
authors.lastname: Renart
authors.forename: Elisa
authors.initials: E
authors.lastname: Carrasco
authors.forename: María
authors.initials: M
authors.lastname: Calvo
authors.forename: Angeles
authors.initials: A
authors.lastname: Juarranz
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D021581:Active Transport, Cell Nucleus; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015536:Down-Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017384:Sequence Deletion; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human