On the trail of cardiac specific transcription factors.

See article by Dellow et al. [1] (pages 24–33) in this issue. Transcription factors are the last link in signaling cascades regulating gene transcription. An increasing number of transcription factors have been described over the last years, and for many genes, essential transcription factor binding regions have been identified. The detailed understanding of the promoter regions essential for gene transcription and the different transcription factors, which are involved in promoter activation, is one of the scientific challenges of this decade and a prerequisite for targeted interventions in gene expression. In this context, the discovery of organ and gene specific transcription factors are of particular interest. In this issue of Cardiovascular Research [1], the group of Paul J.R. Barton reports on recent progress in their efforts to define the essential activation sites of the human cardiac troponin I promoter. This promoter is interesting for cardiovascular research because troponin I is one of the few sarcomeric proteins, which are exclusively expressed in cardiac muscle. One might speculate that this promoter will be useful for the development of cardiac specific targeting vectors, which might be used in future gene therapy of cardiac muscle diseases. In a previous report Bhavsar et al. demonstrated that a minimal 98 bp containing promoter segment is sufficient to initiate human troponin I gene expression [2]. Within this compact region GATA-4, MEF2/Oct-1, Sp1 and CACC box-binding factors are required for optimal gene activation. These recent findings are in accordance with an earlier report by Di Lisi et al. [3] who demonstrated that binding sites specific for Sp1, MEF2/Oct-1 and GATA are necessary for activation of the mouse cardiac troponin I promoter. In this issue, Barton's group describes two potentially novel cardiac specific transcription factors, which bind to the CACC/Sp1-box element and seem to be essential for troponin … * Tel.: +1-713-794-7949; fax: +1-713-794-7770 mflesch{at}bcm.tmc.edu