InterPro domain: IPR009044

This superfamily represents a ssDNA-binding transcriptional regulator domain consisting of a helix-swapped dimer of beta(4)-alpha motifs. This domain is found as a C-terminal domain in the transcriptional co-activator PC4 (also known as P15; where it is a dimer of two separate motifs), and in the plant transcriptional regulator PBF-2 (where it is a single chain domain formed by a tandem repeat of two motifs).

Transcriptional regulators play a critical role in controlling the level of transcription from specific genes in response to different stimuli. Members of this family of transcriptional regulators, which preferentially bind single-stranded DNA, include PBF-2 from plants, the mammalian nuclear factor 1-X (NF1-X), and positive cofactor 4 (PC4). These proteins are structurally similar, consisting of a helix-swapped dimer of beta(4)-alpha motifs.

The plant defence transcription factor PBF-2 is comprised of four p24 subunits that interact through a helix-loop-helix motif to produce a central pore [ 1 ]. PBF-2 functions as part of the plant's defence system in response to the detection of a pathogen. Upon stimulation, PBF-2 induces several signal transduction pathways leading to changes in the expression of defence genes, including the pathogenesis-related (PR) genes.

NF1-X is one of several NF1 proteins that function as transcription factors. NF1-X consists of two functionally distinct domains: a conserved N-terminal DNA-binding domain and a C-terminal transcriptional regulatory domain. NF1-X binds to the promoter for the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase gene [ 2 ].

PC4 (or P15) possess the ability to co-activate and suppress transcription via its DNA-binding activity. PC4 has been shown to stimulate transcription in vitro with diverse activators, including VP16, thyroid hormone receptor, BRCA-1, often involving TFIIA. PC4 and TFIIA are thought to facilitate the assembly of the pre-initiation complex. The repressive activity of PC4 can be alleviated by the transcription factor TFIIH, which protects promoters from PC4 repression [ 3 ]. PC4 consists of two domains: an N-terminal regulatory domain and a C-terminal cryptic DNA-binding domain. The protein acts as a dimer with two ssDNA binding channels running in opposite directions to each other [ 4 ].

1. A new family of plant transcription factors displays a novel ssDNA-binding surface. Nat. Struct. Biol. 9, 512-7
2. Expression, DNA-binding specificity and transcriptional regulation of nuclear factor 1 family proteins from rat. Biochem. J. 342 ( Pt 1), 189-98
3. Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH. J. Biol. Chem. 278, 14827-31
4. C-terminal domain of transcription cofactor PC4 reveals dimeric ssDNA binding site. Nat. Struct. Biol. 4, 900-3