First Time, Every Time: Nucleosomes at a Promoter Can Determine the Probability of Gene Activation
Warren P. Voth1 and David J. Stillman1, Corresponding Author Contact Information, E-mail The Corresponding Author
1 Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA
Available online 19 April 2010.
Transcription factor binding sites are found in either nucleosome-free or nucleosome-embedded locations, thus in vivo relationships between nucleosome position and gene activation are not fully understood. In this issue of Developmental Cell, Bai et al. show that binding sites located in nucleosome depleted regions guarantee high reliability, not amplitude, of promoter firing.
A nucleosome can block transcription factor binding, and global surveys show most promoters have upstream nucleosome depleted regions (NDRs), while others have nucleosomes that may block transcription factor binding. What are the effects of inhibitory nucleosomes on gene activation? In this issue of Developmental Cell, Bai et al. (2010) examine this question at a cell-cycle regulated promoter and show that a promoter NDR can guarantee that a gene is activated every cycle. Alternatively, nucleosome-occupied binding sites can create a bimodal pattern of activation that may require stricter conditions for activation.
The S. cerevisiae CLN2 gene encodes a G1 cyclin, and cyclin expression drives the G1/S transition (Skotheim et al., 2008). Bai et al. (2010) mapped positions of nucleosomes at the CLN2 promoter and found a nucleosome covering the TATA element and the transcription start site (Figure 1A). The NDR between nucleosomes −2 and −3 contains three binding sites for SBF, a G1-specific transcription factor. SBF is inactive in early G1, but phosphorylation of the Whi5 inhibitor by CDK1 ends this inhibition, allowing SBF to activate CLN2 ([Costanzo et al., 2004] and [de Bruin et al., 2004]). Studies with synchronized cells show that nucleosomes −1 and −2 are evicted transiently during the cell-cycle and that nucleosome eviction requires SBF and the FACT histone chaperone ([Bai et al., 2010] and [Takahata et al., 2009a]).