Repression of TFII-I-dependent transcription by nuclear exclusion

doi:10.1073/pnas.141222298

Repression of TFII-I-dependent transcription by nuclear exclusion

^*Department of Pathology, ^‡Programs in Immunology and Genetics, and ^§Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111; and ^†Department of Molecular, Cellular, and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520

Contributed by Frank H. Ruddle

Abstract

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 functions of TFII-I by controlling its nuclear residency. MusTRD1/BEN has five or six direct repeats, each containing helix–loop–helix motifs, and, thus, belongs to the TFII-I family of transcription factors. TFII-I and MusTRD1/BEN, when expressed individually, show predominant nuclear localization. However, 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 activation of the c-fos promoter. Mutation of a consensus nuclear localization signal in MusTRD1/BEN results in a reversal of nuclear residency of the two proteins and a concomitant gain of c-fos promoter activity. These data suggest a means of transcriptional repression by competition at the level of nuclear occupancy.

Footnotes

↵ ¶ To whom reprint requests should be sent at: § address. E-mail: ananda.roy{at}tufts.edu.
Abbreviations:

MusTRD1,

muscle TFII-I repeat domain-containing protein 1;

GFP,

green fluorescent protein;

HLH,

helix–loop–helix;

NLS,

nuclear localization signal;

GST,

glutathione S-transferase