Identification of a novel Sp1 splice variant as a strong transcriptional activator

► Identification of a new Sp1 splicing isoform called Sp1c. ► Sp1c lacks 48 amino acids in the inhibitory domain. ► Sp1c is generated by exclusion of a short domain (α domain). ► Sp1c is ubiquitously expressed at very low levels. ► Sp1c displays higher transcriptional activity than wild-type Sp1. The transcription factor Sp1 regulates expression of numerous genes involved in many cellular processes. Different post-transcriptional modifications can influence the transcriptional control activity and stability of Sp1. In addition to these modifications, alternative splicing isoforms may also be the basis of its distinct functional activities. In this study, we identified a novel alternative splice isoform of Sp1 named Sp1c. This variant is generated by exclusion of a short domain, which we designate α, through alternative splice acceptor site usage in the exon 3. The existence of this new isoform was confirmed in vivo by Western blotting analysis. Although at very low levels, Sp1c is ubiquitously expressed, as seen in its full-length Sp1. A preliminary characterization of Sp1c shows that: (a) Sp1c works as stronger activator of transcription than full-length Sp1; (b) percentage of HEK293 Sp1c-overexpressing cells is higher in G1 phase and lower in S phase than percentage of HEK293 Sp1-overexpressing cells.