Defective binding of transcriptional repressor ZEB via DNA methylation contributes to increased constitutive levels of p73 in Fanconi anemia cells.
Little is known about the molecular mediators of the Fanconi anemia (FA) pathway involved in the machinery that maintains genomic integrity. Here, we report that the levels of p73 and its target genes, are increased in cells derived from FA patients belonging to complementation group A (FA-A). Moreover, functional correction of FA-A cells by gene transfer reduces the expression of p73. We also demonstrate that DNA methylation contributes to increased levels of p73 in FA-A cells by hampering the binding of the transcriptional repressor ZEB to an intronic regulatory region of the p73 gene. Together, our data may help explain the susceptibility of these cells to DNA damaging agents.
Pipaon
Carlos
C
Unidad de Genética Molecular, Hospital Universitario Marques de Valdecilla, Edificio Escuela Universitaria de Enfermeria, Servicio Cantabro de Salud, Av. Valdecilla s/n, 39008 Santander, Spain.
Real
Pedro J
PJ
Fernandez-Luna
Jose L
JL
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D051766:Early Growth Response Protein 1; D005199:Fanconi Anemia / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D051856:Fanconi Anemia Complementation Group Proteins; D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1