1: Int Immunol. 2003 Apr;15(4):467-75. MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators? Jabrane-Ferrat N, Nekrep N, Tosi G, Esserman L, Peterlin BM. Department of Surgery and Comprehensive Cancer Center, University of California San Francisco, CA 94115-0703, USA. MHC class II (MHCII) determinants play a crucial role in the immune response by presenting antigenic peptides to T cells. Their expression is controlled from compact promoters at the transcriptional level. Pre-assembled regulatory factor X (RFX) and nuclear factor Y (NFY) complexes form a platform on DNA. The class II transactivator (CIITA) can then be recruited through multiple protein-protein interactions. In this report, we defined domains of CIITA that are responsible for its interactions with these DNA-bound factors. Furthermore, using DNA-affinity precipitation, we demonstrated that although CIITA binds at least five activators, RFX5, RFXAP, RFXANK/B, NFYB and NFYC, its assembly on the promoter requires the addition of nuclear extracts. We conclude that not only does the platform bind DNA via multiple, spatially constrained nteractions, but that it can recruit only modified and/or complexed CIITA to MHCII promoters. PMID: 12663676 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: J Biol Chem. 2003 Jan 10;278(2):1336-45. Epub 2002 Oct 24. The NF-YB/NF-YC structure gives insight into DNA binding and transcription regulation by CCAAT factor NF-Y. Romier C, Cocchiarella F, Mantovani R, Moras D. Departement de Biologie et Genomique Structurales, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite Louis Pasteur, 1 Rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. The heterotrimeric transcription factor NF-Y recognizes with high specificity and affinity the CCAAT regulatory element that is widely represented in promoters and enhancer regions. The CCAAT box acts in concert with neighboring elements, and its bending by NF-Y is thought to be a major mechanism required for transcription activation. We have solved the structure of the NF-YC/NF-YB subcomplex of NF-Y, which shows that the core domains of both proteins interact through histone fold motifs. This histone-like pair is closely related to the H2A/H2B and NC2alpha/NC2beta families, with features that are both common to this class of proteins and unique to NF-Y. The structure together with the modeling of the nonspecific interaction of NF-YC/NF-YB with DNA and the full NF-Y/CCAAT box complex highlight important structural features that account for different and possibly similar biological functions of the transcriptional regulators NF-Y and NC2. In particular, it emphasizes the role of the newly described alphaC helix of NF-YC, which is both important for NF-Y trimerization and a target for regulatory proteins, such as MYC and p53. PMID: 12401788 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------