Abstract
SummaryTranscription factors (TFs) and histone octamers are two abundant classes of DNA binding proteins that coordinate the transcriptional program in cells. Detailed studies of individual TFs have shown that TFs bind to nucleosome-occluded DNA sequences and induce nucleosome disruption/repositioning, while recent global studies suggest this is not the only mechanism used by all TFs. We have analyzed to what extent the intrinsic DNA binding preferences of TFs and histones play a role in determining nucleosome occupancy, in addition to nonintrinsic factors such as the enzymatic activity of chromatin remodelers. The majority of TFs in budding yeast have an intrinsic sequence preference overlapping with nucleosomal histones. TFs with intrinsic DNA binding properties highly correlated with those of histones tend to be associated with gene activation and might compete with histones to bind to genomic DNA. Consistent with this, we show that activators induce more nucleosome disruption upon transcriptional activation than repressors.
Highlights
Transcription factors (TFs) provide specificity to the transcriptional machinery through the recognition of particular DNA sequences, enabling them to control expression of target genes
Because the binding event depends on the sequence preference between TF and DNA, and is not influenced by other DNA-binding proteins, we regard this as the ‘‘intrinsic’’ DNAbinding preference
For TFs, intrinsic binding sequences were obtained from two large-scale protein binding microarray (PBM) studies (Badis et al, 2008; Zhu et al, 2009), where purified TFs were assayed for binding to custom-designed double-stranded DNA arrays (Berger et al, 2006) (201 position weight matrices [PWMs] among 137 unique TFs in total, Figure 1A)
Summary
Transcription factors (TFs) provide specificity to the transcriptional machinery through the recognition of particular DNA sequences, enabling them to control expression of target genes. The level of transcription largely depends on the binding strength of RNA polymerases and TFs to DNA (Wade et al, 2005). Genomic DNA sequences occluded by nucleosomes are less accessible, which prevents TFs from freely interacting with their cognate sites on DNA due to steric hindrance (Struhl, 1999). Liu and coworkers (Liu et al, 2006) have shown that the computational prediction of in vivo binding of Leu, a Saccharomyces cerevisiae TF, significantly improved when nucleosome occupancy was taken into account. The prediction of sites bound by purified Leu in vitro did not improve, even though the binding motifs are indistinguishable in vivo and in vitro. This study underlined the global role of nucleosomes in determining the pattern of TF binding in living cells
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