Differential Role of the Proline-rich Domain of Nuclear Factor 1-C Splice Variants in DNA Binding and Transactivation

Abstract

Regulation of transcription operates by the combinatorial action of sequence-specific trans-acting factors bound to upstream regulatory regions of promoters and enhancer/silencer regions. The particular linear disposition of these cis-regulatory sequences and their topological organization in chromatin, along with the cellular repertoire of transcription factors results in the formation of gene-and cell-specific constellations of chromatin bound factors. The particular array of proteins on the chromatin target modulates the transcriptional rates by multiple interactions with chromatin remodeling complexes, co-regulators, and components of the basal transcriptional machinery (1). Transcriptional regulators often exhibit a modular structure with independent DNA-binding domains (DBDs) 1 and regulatory regions. The transactivation domains are classified according to their amino acid composition as either rich in acidic side chains, glutamine, or proline residues (2). Although the precise fashion by which transactivators regulate transcription of a specific gene depends on many different promoter features and cell-specific factors, the mechanisms of action for acidic and proline-rich domains appear to be conserved in eukaryotic organisms from yeast to man (3,4).Most transcription factors are expressed in several variants that can be grouped in large families, whose members show only subtle differences. The expression of these variants is tightly regulated in a cell-type or developmental-stage specific manner. Alternative splicing is the mechanism most widely used to generate this precisely regulated, diversity of transcription factors. However, with few exceptions, the functional significance of transcription factor variants generated by alternative splicing is poorly understood (5, 6).

Arabidopsis AtSPL14, a plant‐specific SBP‐domain transcription factor, participates in plant development and sensitivity to fumonisin B1

“…The prevalent proline, serine, and threonine residues (approximately 20%) might comprise a transcriptional activation domain functionally similar to those described for some mammalian transcription factors (Liu et al. , 2003; Prado et al. , 2002).…”

Chromatin-Mediated Restriction of Nuclear Factor 1/CTF Binding in a Repressed and Hormone-Activated Promoter In Vivo

“…Previous studies have shown that NF1 stimulates hormone receptor-mediated MMTV transcription both in vitro (17) and in vivo (9,11,12,40,47). Prado et al (40) used Saccharomyces cerevisiae cells to demonstrate that hormoneinduced MMTV transcription is stimulated by the same porcine NF1-C1 protein as that used in our work and that a mutant MMTV promoter having a relaxed chromatin structure displayed a different mode of NF1 and GR synergy. It was thus astonishing to us that NF1 lacked significant effects on MMTV transcription in our experiments using Xenopus oocytes.…”

Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus

“…Exon 6 repeats forming the insertion/deletion polymorphism encode for the proline‐rich region. Such structures, often present in transcription factors, may define the variety and affinity of other cofactors during transcription activity (14–16). Whether and how the insertion/deletion in the IRF5 gene influences gene function remain to be shown.…”