CIITA STIMULATION OF TRANSCRIPTION FACTOR-BINDING TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II AND ASSOCIATED PROMOTERS IN-VIVO

CIITA is a master transactivator of the major histocompatibility compl ex class II genes, which are involved in antigen presentation. Defects in CIITA result in fatal immunodeficiencies. CIITA activation is also the control point for the induction of major histocompatibility compl ex class II and associated genes by interferon-gamma, but CIITA does n ot bind directly to DNA, Expression of CIITA in G3A cells, which lack endogenous CIITA, followed by in vivo genomic footprinting, now reveal s that CIITA is required for the assembly of transcription factor comp lexes on the promoters of this gene family, including DRA, Ii, and DMB . CIITA-dependent promoter assembly occurs in interferon-gamma-inducib le cell types, but not in B lymphocytes. Dissection of the CIITA prote in indicates that transactivation and promoter loading are inseparable and reveal a requirement fora GTP binding motif. These findings sugge st that CIITA mag be a ne cv class of transactivator.