Broad Institute of MIT and Harvard, Cambridge, MA 02142.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7222-E7230. doi: 10.1073/pnas.1804663115. Epub 2018 Jul 9.
Gene expression is controlled by sequence-specific transcription factors (TFs), which bind to regulatory sequences in DNA. TF binding occurs in nucleosome-depleted regions of DNA (NDRs), which generally encompass regions with lengths similar to those protected by nucleosomes. However, less is known about where within these regions specific TFs tend to be found. Here, we characterize the positional bias of inferred binding sites for 103 TFs within ∼500,000 NDRs across 47 cell types. We find that distinct classes of TFs display different binding preferences: Some tend to have binding sites toward the edges, some toward the center, and some at other positions within the NDR. These patterns are highly consistent across cell types, suggesting that they may reflect TF-specific intrinsic structural or functional characteristics. In particular, TF classes with binding sites at NDR edges are enriched for those known to interact with histones and chromatin remodelers, whereas TFs with central enrichment interact with other TFs and cofactors such as p300. Our results suggest distinct regiospecific binding patterns and functions of TF classes within enhancers.
基因表达受序列特异性转录因子 (TFs) 的控制，这些因子与 DNA 中的调节序列结合。TF 结合发生在核小体缺失的 DNA 区域 (NDRs) 中，这些区域通常包含与核小体保护的区域长度相似的区域。然而，对于这些区域中特定的 TFs 倾向于在哪里发现，人们知之甚少。在这里，我们描述了在 47 种细胞类型中，约 500,000 个 NDR 中 103 个 TFs 的推断结合位点的位置偏好。我们发现，不同类别的 TFs 表现出不同的结合偏好：有些倾向于在 NDR 的边缘具有结合位点，有些倾向于在中心，有些则在 NDR 内的其他位置具有结合位点。这些模式在细胞类型之间高度一致，表明它们可能反映了 TF 特异性的内在结构或功能特征。特别是，在 NDR 边缘具有结合位点的 TF 类富含已知与组蛋白和染色质重塑剂相互作用的 TF，而具有中央富集的 TF 与其他 TF 和辅助因子（如 p300）相互作用。我们的结果表明，在增强子中，TF 类具有不同的区域特异性结合模式和功能。
