BOCCO JOSE LUIS
Congresos y reuniones científicas
Título:
Transcriptional Control of the Human KLF6 Gene.
Autor/es:
GEHRAU, RICARDO; D’ASTOLFO, DIEGO; BOCCO, JOSE LUIS; KORITSCHONER, NICOLAS
Lugar:
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular.
Reunión:
Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular. 10th Congress Panamerican Association for Biochemistry and Molecular Biology. 20th Reunión Anual Sociedad Argentina de Neuroquímica; 2005
Institución organizadora:
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Resumen:
KLF6 is regulated during cell proliferation and differentiation events while its aberrant expression is associated with tumor formation. Genomic organization and cis-regulatory regions of KLF6 were analyzed to investigate its transcriptional control. Sequence alignments showed a high homology of KLF6 regulatory regions in mammals that predicts evolutionary conserved transcriptional mechanisms. Primer extension assays identified a transcription start site in the vicinity of a potential Initiator element. Reporter constructs of the 5 ´flanking region were used to determine KLF6 regulatory elements by transfection assays. A minimal promoter region lacking a functional TATA-box yet containing an Initiator was identified and found to be active in all cell lines analyzed. Also, two strong activating sequences (-407/-344 and -307/-207)were identified where the latter contains Sp1 sites. Ectopic expression of Sp1 increased KLF6 transcriptional activity. Additionally, DNA damaging agents provoked a significant increase of KLF6 promoter activity in p53-null cells (Hep3B),while an opposite effect was observed in p53-wt cells (HepG2). In conclusion,KLF6 gene transcription is under control of a TATA-box less initiation mechanism together with an evolutionary conserved array of positive cis-acting elements. Also, the KLF6 promoter activity was responsive, depending on the p53 status, to a variety of chemotherapeutic agents.
