ARID3a/Bright is a DNA-binding protein that was originally discovered for its ability to increase immunoglobulin transcription in antigen-activated B cells. It interacts with DNA as a dimer through its ARID, or A/T-rich interacting domain. In association with other proteins, ARID3a increased transcription of the immunoglobulin heavy chain and led to improved chromatin accessibility of the heavy chain enhancer. Constitutive expression of ARID3a in B lineage cells resulted in autoantibody production, suggesting its regulation is important. Abnormal ARID3a expression has also been associated with increased proliferative capacity and malignancy. Roles for ARID3a in addition to interactions with the immunoglobulin locus were suggested by transgenic and knockout mouse models. Over-expression of ARID3a resulted in skewing of mature B cell subsets and altered gene expression patterns of follicular B cells, whereas loss of function resulted in loss of B1 lineage B cells and defects in hematopoiesis. More recent studies showed that loss of ARID3a in adult somatic cells promoted developmental plasticity, alterations in gene expression patterns, and lineage fate decisions. Together, these data suggest new regulatory roles for ARID3a. The genes influenced by ARID3a are likely to play pivotal roles in lineage decisions, highlighting the importance of this understudied transcription factor.
Keywords: Bright, ARID3a, hematopoietic regulation, B cell development, gene regulationBright (B cell regulator of immunoglobulin heavy chain transcription) is a 70 kDa DNA-binding protein first characterized in the mouse as a component of a protein complex associated with increased transcription of the immunoglobulin heavy chain (IgH) locus in activated B lymphocytes (1-3). Bright, also known as DRIL1, E2FBP1, or ARID3a (the designation for the human ortholog, hereafter referred to as Bright), is a member of the A + T rich interaction domain (ARID) protein family, many of which have been shown recently to have epigenetic regulatory functions [reviewed in ]. These proteins bind to A + T rich DNA sequences and are typically members of larger chromatin modulatory complexes. Bright, and other ARID3 family members, require dimerization for DNA-binding activity and contain an extended DNA-binding domain that confers increased DNA sequence specificity to these proteins compared to other ARID family members (7-9). Although Bright was the first member of this family identified in mammalian cells, its functions have only begun to be elucidated. Previously, Bright expression in adult, mouse, and human cells was thought to be largely restricted to B lymphocyte lineage cells. However, more recently, we and others have shown that Bright plays important regulatory functions in early hematopoiesis. Although Bright expression is restricted in adults, it is more widely expressed in the embryo/fetus and plays important regulatory roles in embryonic stem cell differentiation (10). These data also highlight novel roles for Bright in gene repression. This artic...