Nucleic Acids Research, Vol 26, Issue 18 4128-4136, Copyright © 1998 by Oxford University Press
JA Brown, EM Rogers and JM Boss
The class II transactivator CIITA is required for transcriptional
activation of the major histocompatibility complex (MHC) class II genes.
Aside from an N-terminal acidic transcriptional activation domain, little
is known about how this factor functions. Extensive mutagenesis of CIITA
was undertaken to identify structural motifs required for function. The
ability of mutants to activate a reporter gene under the control of MHC
class II conserved W-X-Y or X-Y regulatory elements was determined. Two
mutants displayed differential activity between the two promoters,
activating transcription with the W- X-Y but not the X-Y elements. All
mutants were tested for their ability to interfere with wild-type CIITA
activity. Five CIITA mutant constructions were able to down-regulate
wild-type CIITA activity. Three of these mutants contained targeted
disruptions of potential functional motifs: the acidic activation domain, a
putative GTP-binding motif and two leucine charged domains (LCD motifs).
The other two contained mutations in regions that do not have homology to
described proteins. The characterization of CIITA mutants that are able to
discriminate between promoters with or without the W box strongly suggests
that CIITA requires such interactions for function. The identification of
LCD motifs required for CIITA function brings to light a previously
undefined role of these motifs in CIITA function.
ARTICLES
The MHC class II transactivator (CIITA) requires conserved leucine charged domains for interactions with the conserved W box promoter element
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
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