Repression of TFII-I-dependent transcription by nuclear exclusion

TFII-I is an unusual transcription factor possessing both basal and signal- induced transcriptional functions. Here we report the characterization of a TFII-I-related factor (MusTRD1 /BEN) that regulates transcriptional functi ons of TFII-I by controlling its nuclear residency. MusTRD1/BEN has five or six direct repeats, each containing helix-loop-helix motifs, and, thus, be longs to the TFII-I family of transcription factors. TFII-I and MusTRD1/BEN , when expressed individually, show predominant nuclear localization. Howev er, when the two proteins are coexpressed ectopically, MusTRD1/BEN locates almost exclusively to the nucleus, whereas TFII-I is largely excluded from the nucleus, resulting in a loss of TFII-I-dependent transcriptional activa tion of the E-fos promoter. Mutation of a consensus nuclear localization si gnal in MusTRD1/BEN results in a reversal of nuclear residency of the two p roteins and a concomitant gain of c-fos promoter activity. These data sugge st a means of transcriptional repression by competition at the level of nuc lear occupancy.