A multiplicity of CCAAT box-binding proteins

A Dorn, J Bollekens, A Staub, C Benoist, D Mathis - Cell, 1987 - cell.com
A Dorn, J Bollekens, A Staub, C Benoist, D Mathis
Cell, 1987cell.com
NF-Y is a sequence-specific DNA-binding protein that recognizes the Y box, a promoter
element common to ail major hist~ om~ tibiii~ complex class ii genes. Since the 1Gbase Y
element harbors a CCAAT box in reverse, we were prompted to ask whether NFY is actuafiy
a CCAAT box-binding protein and whether it is related to the previously described CCAAT-
binding factors CBP and CTF/NF-I. Data from gel retardation, methyiation interference,
saturation mutagenesis, and cross-competition experiments establish definitively that NF-Y …
Summary
NF-Y is a sequence-specific DNA-binding protein that recognizes the Y box, a promoter element common to ail major hist~ om~ tibiii~ complex class ii genes. Since the 1Gbase Y element harbors a CCAAT box in reverse, we were prompted to ask whether NFY is actuafiy a CCAAT box-binding protein and whether it is related to the previously described CCAAT-binding factors CBP and CTF/NF-I. Data from gel retardation, methyiation interference, saturation mutagenesis, and cross-competition experiments establish definitively that NF-Y is an entiraiy distinct CCAAT box-binding entity. Moreover, these experiments have uncovered a fourth CCAAT-binding protein, NF-Y’, that interacts with the thymidine kinase promoter. Clearly, then, there exists a multiplici~ of factors that recognize CCAAT sequences; it now becomes imperative to understand the functional significance of this multiplicity. introduction
The class II genes of the major histocompatibility complex (MHC) are expressed in an elaborately controlled fashion (for reviews, see Frelinger, 1982; Flavell et al., 1985). Thus murine class II molecules are essentially confined to cells that function in the immune system: macrophages and other antigen presenters, mature B cells, and thymic epithelial and dendritic cells. Expression within a single lineage can fluctuate with differentiation events: in the B lineage, for example, murine class II genes are silent in pre-B cells, are transcribed actively in more mature B descendants, and are shut off in terminally differentiated plasma cells. Finally, the class ii genes can be regulated by a variety of effecters that act with cell-type specificity: y interferon in macrophages, interleukin~ in B cells. The significance of these elaborate controls is underlined by the observation that inappropriate class II gene expression may engender autoimmune disease (Bottazro et al., 1983; Waksman, 1985).
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