Article

Mutations in the DNA-binding domain of the transcription factor Bright act as dominant negative proteins and interfere with immunoglobulin transactivation.

Oklahoma Medical Research Foundation, 825 N. E. 13 Street, Oklahoma City, Oklahoma 73104, USA.
Journal of Biological Chemistry (impact factor: 4.77). 01/2005; 279(50):52465-72. DOI:10.1074/jbc.M403028200 pp.52465-72
Source: PubMed

ABSTRACT Bright, for B cell regulator of immunoglobulin heavy chain transcription, binds A+T-rich sequences in the intronic enhancer regions of the murine heavy chain locus and 5'-flanking sequences of some variable heavy chain promoters. Most resting B cells do not express Bright; however, it is induced after stimulation with antigen or polyclonal mitogens. Bright activation results in up-regulation of mu transcription; however, it is not clear whether Bright function is critical for normal B cell development. To begin to address Bright function during B cell development, seven mutated forms of Bright were produced. Five of the seven mutants revealed little or no DNA binding activity. Furthermore, because Bright binds DNA as a dimer, two of the mutants formed complexes with wild type Bright and acted in a dominant negative fashion. Dominant negative Bright prevented the up-regulation of mu transcription in transfected Chinese hamster ovary cells transfected with wild type Bright. These data identify regions within Bright that are required for the DNA binding activity of Bright and for its function as a transcription factor.

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Keywords

address Bright function
 
B cell development
 
B cell regulator
 
binds A+T-rich sequences
 
Bright activation results
 
Bright binds DNA
 
Bright function
 
DNA binding activity
 
Dominant negative Bright
 
dominant negative fashion
 
immunoglobulin heavy chain transcription
 
intronic enhancer regions
 
mu transcription
 
murine heavy chain locus
 
normal B cell development
 
resting B cells
 
transcription factor
 
transfected Chinese hamster ovary cells transfected
 
variable heavy chain promoters
 
wild type Bright