Studies on Multiple Homeodomain/Zn Finger ATBF1 Gene Family

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The ATBF1(AT motif binding factor 1)cDNA was isolated based on the ability of its product to bind to an AT-rich enhancer element of the human alpha-fetoprotein(AFP)gene. This transcription factor is characterized by a large size(>300kd)and presence of many DNA-binding domains(4 homeotic-domain, 22 Zn-finger structure). This protein also contains many other functional domain structures, such as acidic-domain, glutamine-rich domain, ATP-ase-like domain and kination sequence.To understand the structure, expression and physiological functions of this interesting protein, we collaborate with members of different fields. The international collaboration was obtained the following results.1.The mouse ATBF1 was cloned and shows 95% homologies with human. The homeotic domains were conserved at 100%.2.Two isoform of the ATBF1(ATBF1-A and ATBF1-B)were expressed from the independent promoters and alternative splicing. The promoter specific for ATBF1-A controls the neural cell expression.3.The results of in situ-hybridization and Northern blotting analysis of P19 cells indicate that the expression of ATBF1 is closely associate with neuronal differentiation.4.ATBF1 genes of human and mouse were mapped on Chromosome 16p22.3-23.1 and 8E1, respectively.5.ATBF1 suppresses the transcription of AFP gene. The required domains for the suppression were located on proline-rich domain and 4th homeotic-domain.6.We have obtained many other interesting properties of ATBF1, i.e., ATBF1 functions as a dimer, ATBF1 might be processed in nucleus and ATBF1 worked as a suppressor of the cell growth.For keep the close contacts between collaborators and exchange the information, 12 researchers visited to Canada and 4 researchers invited to Japan within 2 years. This collaboration was very successfully functioned and made excellent results as described above.