The orientation of the AP-1 heterodimer on DNA strongly affects transcriptional potency

Activation of gene transcription in eukaryotes requires the cooperative assembly of an initiation complex containing many protein subunits. The necessity that these components contact each other and the promoter/enhancer in defined ways suggests that their spatial arrangement might influence the activation response. Indeed, growing evidence indicates that DNA architecture can profoundly affect transcriptional potency. Much less is known about the influence of protein architecture on transcriptional activation. Here, we examine the architectural dependence of activator function through the analysis of matched pairs of AP-1•DNA complexes differing only in their orientation. Mutation of a critical Arg residue in the basic-leucine zipper domain of either Fos or Jun yielded single point-mutant heterodimers that bind DNA in a single defined orientation, as determined directly by native chemical ligation/affinity cleavage; by contrast, the corresponding wild-type protein binds DNA as a roughly equal mixture of two isomeric orientations, which are related by subunit interchange. The stereochemistry of the point-mutant heterodimers could be switched by inversion of a C•G base pair in the center of the AP-1 site, thus providing access to both fixed orientational isomers. Yeast reporter gene assays consistently revealed that one orientational isomer activates transcription at least 10-fold more strongly than the other. These results suggest that protein architecture, especially the spatial relationship of the activation domain to the promoter, can exert a powerful influence on activator potency.

Raising the bar: the importance of hospital library standards in the continuing medical education accreditation process*

The Connecticut State Medical Society (CSMS) reviews and accredits the continuing medical education (CME) programs offered by Connecticut's hospitals. As part of the survey process, the CSMS assesses the quality of the hospitals' libraries. In 1987, the CSMS adopted the Medical Library Association's (MLA's) “Minimum Standards for Health Sciences Libraries in Hospitals.” In 1990, professional librarians were added to the survey team and, later, to the CSMS CME Committee. Librarians participating in this effort are recruited from the membership of the Connecticut Association of Health Sciences Librarians (CAHSL). The positive results of having a qualified librarian on the survey team and the invaluable impact of adherence to the MLA standards are outlined. As a direct result of this process, hospitals throughout the state have added staffing, increased space, and added funding for resources during an era of cutbacks. Some hospital libraries have been able to maintain a healthy status quo, while others have had proposed cuts reconsidered by administrators for fear of losing valuable CME accreditation status. Creating a relationship with an accrediting agency is one method by which hospital librarians elsewhere may strengthen their efforts to ensure adequate library resources in an era of downsizing. In addition, this collaboration has provided a new and important role for librarians to play on an accreditation team.