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. 2008 Dec 26;32(6):878-87.
doi: 10.1016/j.molcel.2008.11.020.

A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters

Gwenael Badis  1 , Esther T Chan, Harm van Bakel, Lourdes Pena-Castillo, Desiree Tillo, Kyle Tsui, Clayton D Carlson, Andrea J Gossett, Michael J Hasinoff, Christopher L Warren, Marinella Gebbia, Shaheynoor Talukder, Ally Yang, Sanie Mnaimneh, Dimitri Terterov, David Coburn, Ai Li Yeo, Zhen Xuan Yeo, Neil D Clarke, Jason D Lieb, Aseem Z Ansari, Corey Nislow, Timothy R Hughes
Affiliations

A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters

Gwenael Badis et al. Mol Cell. .

Abstract

The sequence specificity of DNA-binding proteins is the primary mechanism by which the cell recognizes genomic features. Here, we describe systematic determination of yeast transcription factor DNA-binding specificities. We obtained binding specificities for 112 DNA-binding proteins representing 19 distinct structural classes. One-third of the binding specificities have not been previously reported. Several binding sequences have striking genomic distributions relative to transcription start sites, supporting their biological relevance and suggesting a role in promoter architecture. Among these are Rsc3 binding sequences, containing the core CGCG, which are found preferentially approximately 100 bp upstream of transcription start sites. Mutation of RSC3 results in a dramatic increase in nucleosome occupancy in hundreds of proximal promoters containing a Rsc3 binding element, but has little impact on promoters lacking Rsc3 binding sequences, indicating that Rsc3 plays a broad role in targeting nucleosome exclusion at yeast promoters.

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Figures

Fig 1
Fig 1
Motifs identified in our study.
Fig 2
Fig 2. Comparison of motif representation and reproducibility of 8-mer profiles across platforms
(A) PWM scores (Granek and Clarke, 2005) for all possible 8-mers for the single motif with highest Pearson correlation to the PBM 8-mers, plotted against the Z-scores from the PBM. (B) CSI Z-scores (combined from up to four array spots containing the 8-mer) vs. Z-scores from PBM. Data are plotted as asinh values, which are similar to natural log, but return real values for negative numbers (by definition, half of all Z-scores are negative).
Fig 3
Fig 3. Similarity among C2H2 zinc finger motifs reflects DNA-binding domain sequence similarity
The phylogram tree was created using online EBI ClustalW with default settings. Our motifs are shown next to the gene names; inconsistent motifs from (MacIsaac et al., 2006) are shown for Stp4 and Yml081w. Yellow asterisks represent pairs arising from the WGD. Colors of protein names reflect our classifications of consistency with prior data: Green; known motif obtained; Red; discrepancy between our motif and that previously reported; Yellow, new motif but consistent with expectation based on homology; Blue, new unexpected motif.
Fig 4
Fig 4. Bias in the position of TF binding sequences in 5,015 promoters with well-defined TSS (Lee et al., 2007)
Motif scores (Granek and Clarke, 2005) were calculated for 8-bp windows, and high-scoring 8-mers were tallied along equivalent positions of all of the yeast promoter sequences using a cutoff selected to capture only the linear range of Z vs. PWM score in PBM experiments (cutoff values are given in Supplementary data). Background was calculated from the first 100 bases of yeast ORFs. TFs are sorted by relative enrichment between −125 and −75.
Fig 5
Fig 5. Rsc3 influences nucleosome occupancy at proximal promoters containing Rsc3 binding sites
(A) A segment of Chromosome XIII with a Rsc3 binding sequence (grey vertical line) that is depleted in wildtype but occupied in the rsc3-1 mutant. (B, C) Changes in promoter nucleosome occupancy profiles between rsc3-1 and a wildtype control for promoters containing Rsc3 binding sequences (C), or containing Reb1 binding sequences but not Rsc3 binding sequences (D). Promoters are sorted by the position of the highest scoring Rsc3 or Reb1 binding sequence location in the promoter, which is shown at left in panels B and C. Additional sites of equivalent PWM score are also indicated.
Fig 6
Fig 6. Comparison of the effects of mutations in essential DNA-binding proteins on nucleosome profiles at all promoters
Promoters are sorted by change in occupancy in the NFR. Locations of binding sequences for the mutated factor are illustrated at left, in tiling intervals matching those of the array, and shown as heat-maps. Relative transcript levels are illustrated at right. The rsc3-1 panel (upper left) also shows the change in relative enrichment in Rsc8-TAP ChIP-chip between the rsc3-1 and wildtype strains.
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