Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and the upstream sequence of the Otx2 gene in embryonal carcinoma cells.

The Journal of Biological Chemistry
S GuazziE Boncinelli

Abstract

Vertebrate Hox and Otx genes encode homeodomain-containing transcription factors thought to transduce positional information along the body axis in the segmental portion of the trunk and in the rostral brain, respectively. Moreover, Hox and Otx2 genes show a complementary spatial regulation during embryogenesis. In this report, we show that a 1821-base pair (bp) upstream DNA fragment of the Otx2 gene is positively regulated by co-transfection with expression vectors for the human HOXB1, HOXB2, and HOXB3 proteins in an embryonal carcinoma cell line (NT2/D1) and that a shorter fragment of only 534 bp is able to drive this regulation. We also identified the HOXB1, HOXB2, and HOXB3 DNA-binding region on the 534-bp Otx2 genomic fragment using nuclear extracts from Hox-transfected COS cells and 12.5 days postcoitum mouse embryos or HOXB3 homeodomain-containing bacterial extracts. HOXB1, HOXB3, and nuclear extracts from 12.5 days postcoitum mouse embryos bind to a sequence containing two palindromic TAATTA sites, which bear four copies of the ATTA core sequence, a common feature of most HOM-C/HOX binding sites. HOXB2 protected an adjacent site containing a direct repeat of an ACTT sequence, quite divergent from the ATTA consensus. The...Continue Reading

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Citations

Aug 3, 2005·Cellular and Molecular Neurobiology·Z N Akin, A J Nazarali
Feb 21, 2007·Experimental Hematology·King-Hung KoLiwei Lu
Feb 4, 2003·Journal of Neurochemistry·Virginie CourtoisThomas Lamonerie
Feb 25, 2011·BMC Developmental Biology·Daniel SilberschmidtMario De Felice
Aug 8, 2006·Developmental Cell·Petr Tvrdik, Mario R Capecchi
Mar 23, 2010·Molecular and Cellular Endocrinology·Lucia Montanelli, Massimo Tonacchera
Mar 29, 2003·The Journal of Biological Chemistry·Juan Ramón Martínez-MoralesSimon Saule

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