Functional characterization of the novel a/t-rich interaction domain member, Brightlike (ARID3C)
ARID proteins are highly conserved among eukaryotes and are involved in chromatin remodeling, differentiation and development. The founding member of the ARID3 subfamily, Bright/ARID3A, is an activator of the immunoglobulin heavy chain locus. Bright has been shown to immortalize mouse embryonic fibroblasts and induce malignant transformation when co-expressed with oncogenic Ras. A genomic locus that encodes a gene paralogous to Bright has been identified as Brightlike/ARID3C. In addition to the highly conserved ARID and REKLES domains, Brightlike contains a conserved sumoylation motif. Brightlike orthologous genes have been identified in all vertebrate genomes examined. Its absence from EST databases suggested that it is a rare transcript, and accordingly, its expression in adult mice appears to be restricted to spleen, testes and thymus. Brightlike is also regulated by alternative pre-mRNA splicing, differential subcellular distribution, and post-translational modification by SUMO. The two isoforms of Brightlike appear to have differential expression in lymphocyte populations. Brightlike and Bright bind to the same DNA motif. Unexpectedly, Bright and Brightlike do not form heterocomplexes on DNA nor compete for binding, suggesting they have independent functions in vivo. Brightlike increases the proliferation potential of mouse embryonic fibroblasts and rescues cells from premature senescence, suggestive of a proto-oncogene.