REGULATION OF DIFFERENTIATION BY BACH TRANSCRIPTION FACTORS

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To understand molecular regulation of cell differentiation, it is essential to reveal regulation of transcription in these processes. Bachi and Bach2 are closely related transcription factors that bind to DNA by forming heterodimers with Maf family of transcription factors. During the past two years supported by this grant, we accumulated results that suggested that Bachi and Bach2 are involved in regulation of hematopoiesis, and that they function as a novel type of architectural transcription fadors.(1) The BTB domain of Bach1 and Bach2 appears to be involved in regulation of chromatin structure. Using atomic force microscopy, we revealed that Bach1, and possible Bach2, fundion as a novel type of architectural transcription factor that mediate DNA loop formation. As such, Bach1 may be involved in regulation of the globin gene locus control region.(2) Expression of Bach2 is specific to B cells among hematopoietic cells. Its expression is high during early stages and down regulated upon maturation to plasmacytes. Bach2 represses 3' enhancer of the immunoglobulin heavy chain gene. Thus Bach2 appears to regulate stage-specific gene expression during B cell differentiation.(3) Using yeast two hybrid screen, we isolated a novel transcription factor, FOB (friend of Bach), as aprotein that binds to the BTB domain of Bach. FOB carries the BTB domain as well as a C2H2-typeZn fingers. Expression profile of FOB suggested that it is a partner of Bach1 and/or Bach2 inhematopoietic cells.