TFIIS and GreB Two Like-Minded Transcription Elongation Factors with Sticky Fingers

such as P/CAF and SRC1 (reviewed in Coqueret, 2002) TFIIS and GreB: Two Like-Minded depending on the promoter context, so it will be critical Transcription Elongation Factors to determine the acetylation status of both C/EBP and histones on cyclin D1 target gene promoters. A third with Sticky Fingers important question is why should LIP activate these target genes? Does it merely displace or antagonize the transcriptional activity of the bound LAP isoforms? LIP How the structurally distinct transcription factor TFIIS has been reported to exhibit an increased DNA binding from eukaryotes and its bacterial counterpart GreB affinity relative to the LAP isoforms of C/EBP . Does act to convert their cognate RNA polymerases into this then imply that there is a reciprocal relationship ribonucleases has been a longstanding question. between cyclin D1 and LIP expression in cancer? In Now, two new structures of these factors bound to breast cancers, LIP was reported to be predominantly their respective RNA polymerases (Opalka et al. and overexpressed in ER-negative tumors (Milde-Langosch Kettenberger et al. [this issue of Cell]) suggest how et al., 2003; Zahnow et al., 1997), while cyclin D1 is usually they accomplish this feat. elevated in ER-positive tumors. Curiously, overexpression of the translation initiation factor eIF4e has been shown to increase cyclin D1 expression, while decreased Eukaryotic TFIIS (also known as SII) and its bacterial expression of eIF4e and eIF2 has been correlated with counterpart GreB are unique among all transcription increased LIP expression (Calkhoven et al., 2000). Howfactors: they are the only known transcription factors ever, other mechanisms involving both gene amplificacapable of restarting arrested RNA polymerases (Wind tion and transcriptional activation are involved in the and Reines, 2000; Uptain et al., 1997). TFIIS is expressed overexpression of cyclin D1 in cancer. A more thorough ubiquitously in eukaryotes, where it acts specifically to examination of the mechanisms regulating the expresreactivate arrested RNA polymerase II to ensure efficient sion of different C/EBP isoforms and their activities synthesis of mRNA. GreB performs a similar task in on different target gene promoters is, however, clearly bacteria. warranted. Finally, what are the functions of the specific The tendency to arrest is an inherent property of RNA cyclin D1 target genes identified in this study in the polymerases. Upon arrest, an RNA polymerase stops etiology of cancer? Thus, while numerous interesting transcribing, refuses to budge even in the presence of questions remain to be answered, the future for combinsufficient concentrations of ribonucleoside triphosing molecular genetic and data mining approaches to phates to support further transcript elongation, and discover novel interactions and pathways in human canclings tenaciously to its DNA template and nascent trancer appears bright. script, presenting a potential impediment to other RNA polymerases. Arrest occurs when the 3 -end of a nascent transcript Jeffrey M. Rosen loses critical base pair contacts with the DNA template and is displaced from, or in some cases, completely extruded from the polymerase active site through a pore or channel that is situated directly beneath the primary Department of Molecular and Cellular Biology catalytic magnesium ion and through which incoming Baylor College of Medicine ribonucleoside triphosphates are believed to enter the 1 Baylor Plaza active site (Komissarova and Kashlev, 1997; Nudler et Houston, Texas 77030 al., 1997; Cramer et al., 2000, 2001; Zhang et al., 1999). Elegant biochemical studies have shown that TFIIS and Selected Reading GreB restart arrested RNA polymerases by a remarkable