IL3BP1, A Transcription Factor with Dual Function

Abstract

Transcriptional regulation of eukaryotic gene expression involves interactions between transcription factor proteins and specific DNA sequences in the enhancer/promoter regions of regulated genes. These transcription factors can be activators, which can act by increasing transcription initiation or enhancing mRNA elongation (1), or they can serve as transcriptional suppressors and down regulate transcription (2,3). There are many transcription factors that can function either as activators or suppressors, depending on the context. For example, the Drosophila transcription factor Kruppel functions as an activator at low concentration, by interacting with TFIIB as a monomer, but it functions as a suppressor at high concentration, forming a dimer and interacting with TFIIEß(4). The human thyroid hormone receptor-ß (hTRß) converts from a repressor to an activator upon binding of thyroid hormone, and YY1 suppresses transcription when bound to the initiation region of the promoter but converts to an activator when bound by the adenovirus E1a protein (5).

We recently cloned a transcription factor (NF-IL3A) based on its ability to bind to regulatory sequences in the human interleukin-3 promoter (6). The nearly identical transcription factor E4BP4 was cloned based upon its ability to bind to the adenovirus E4 promoter region (7). This factor, which has been given the name IL3BP1 by the Human Genome Nomenclature Committee (alternately named E4BP4 and NF-IL3A), has been shown to act as a repressor of transcription in HepG2 and HeLa cells (7), act as an activator of interleukin-3 (IL-3) promoter function in T cells (6) and have minimal or a slight repressive effect on gene expression in pre-B cells (8).