The mechanisms of regulation of I-A beta gene expression in the murine major histocompatibility complex by transcriptional repression are reviewed. Active and passive repression mechanisms are presented. The transcription factor PU.1 actively inhibits the expression of I-A beta through the binding to a DNA sequence near the Y box, a cis-element in the promoter necessary for transcription. This interaction probably interferes with the preinitiation complex assembly. NF-Y is a transcription factor that binds to the Y box and has two constituents: NF-YA (that binds weakly to DNA) and NF-YB (that increases the binding of NF-YA to DNA). The dbpA protein represses the expression of I-A beta by a quenching mechanism, forming a complex with NF-YA and the dbpB protein by sequestering the NF-YB protein. A similar mechanism is observed with the glucocorticoid receptor that binds to the X-box binding proteins and inhibits their interaction with the X box. These results are examples of cross-talk between proteins, which may help us to understand the regulation of I-A beta gene expression.