Computational prediction of membrane-tethered transcription factors

Joel Zupicich¹ , Steven E Brenner² and William C Skarnes¹

¹Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720-3200, USA

²Department of Plant and Microbial Biology, University of California at Berkeley, Berkeley, CA 94720-3102, USA

author email corresponding author email

Genome Biology 2001, 2:research0050.1-0050.6doi:10.1186/gb-2001-2-12-research0050


Published:	14 November 2001

Subject areas: Bioinformatics, Cell biology, Biochemistry and structural biology

Abstract

Background

Sequestration of transcription factors in the membrane is emerging as an important mechanism for the regulation of gene expression. A handful of membrane-spanning transcription factors has been previously identified whose access to the nucleus is regulated by proteolytic cleavage from the membrane. To investigate the existence of other transmembrane transcription factors, we analyzed computationally all proteins in SWISS-PROT/TrEMBL for the combined presence of a DNA-binding domain and a transmembrane segment.

Results

Using Pfam hidden Markov models and four transmembrane-prediction programs, we identified with high confidence 76 membrane-spanning transcription factors in SWISS-PROT/TrEMBL. Analysis of the distribution of two proteins predicted by our method, MTJ1 and DMRT2, confirmed their localization to intracellular membrane compartments. Furthermore, elimination of the predicted transmembrane segment led to nuclear localization for each of these proteins.

Conclusions

Our analysis uncovered a wealth of predicted membrane-spanning transcription factors that are structurally and taxonomically diverse, 56 of which lack experimental annotation. Seventy-five of the proteins are modular in structure, suggesting that a single proteolysis may be sufficient to liberate a DNA-binding domain from the membrane. This study provides grounds for investigations into the stimuli and mechanisms that release this intriguing class of transcription factors from membranes.