The transcription factor KLF6 binds in vivo to the Adenovirus E2A promoter and physically interacts with ATF7.

ANDREOLI, VERÓNICA; PRIETO, CLAUDIO; KORISTCHONER, NICOLAS; CHATTON, BRUNO; BOCCO, JOSE LUIS

Pinamar, Buenos Aires. ARGENTINA

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

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular.

Krüppel-like factor 6 (KLF6)is a ubiquitously expressed member of the Krüppel/Sp1-like family of transcription factors sharing three zinc fingers as a signature DNA binding motif with specificity for GC-boxes promoter elements. Current data support a KLF6 function in the regulation of cell proliferation though the target genes for in vivo binding of KLF6 have not been still identified. Putative consensus KLF6 target sites were identified within the E2A transcription unit of Adenovirus neighbouring to the ATF/CRE binding motif as determined by in vitro PCR-assisted binding selection assays. In this work we demonstrate that KLF6 binds to the E2A promoter in vivo by ChIP and Real-time PCR approaches in lung epithelial cells upon Adenovirus infection. Interestingly, expression of endogenous KLF6 protein was modified during the infection course reaching a maximum level after 6 h. and then decreased correlating with enhanced expression of the E1A viral oncoprotein. On the other hand we determined that KLF6 interacts physically with ATF7 whose role in the E2A transcriptional activation has been demonstrated. Thus we provide evidences that the physiological function of KLF6 and ATF7 transcription factors is subverted during Adenovirus infection to assure transcription of viral genes and thereby disturbing their control of normal cell proliferation.