MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators?
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.
Jabrane-Ferrat
Nabila
N
Department of Surgery and Comprehensive Cancer Center, University of California San Francisco, CA 94115-0703, USA.
Nekrep
Nada
N
Tosi
Giovanni
G
Esserman
Laura
L
Peterlin
B Matija
BM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005802:Genes, MHC Class II; D046911:Macromolecular Substances; D008957:Models, Genetic; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D011817:Rabbits; D000071701:Regulatory Factor X Transcription Factors; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; C083728:MHC class II transactivator protein; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C402244:nuclear factor Y