Accessibility control of antigen-receptor variable-region gene assembly: role of cis-acting elements

Antigen receptor variable region genes are assembled from germline variable (V), diversity (D), and joining (J) gene segments. This process requires expression of V(D)J recombinase activity, and "accessibility" of variable gene segments to this recombinase. The exact mechanism by which variable gene segments become accessible during development is not known. However, several studies have shown that cis-acting elements that regulate transcription may also function to regulate accessibility. Here we review the evidence that transcriptional promoters, enhancers, and silencers are involved in regulation of accessibility. The manner in which these elements may combine to regulate accessibility is addressed. In addition, current and potential strategies for identifying and analyzing cis-acting elements that mediate locus accessibility are discussed.