Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, United States.
Department of Genetics, Washington University School of Medicine, St. Louis, United States.
Elife. 2021 Sep 6;10:e67403. doi: 10.7554/eLife.67403.
Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF cone-rod homeobox (CRX) in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity of -regulatory sequences.
增强子和沉默子通常依赖于相同的转录因子（TFs），并且在 TF 结合或染色质状态的基因组分析中被混淆。为了鉴定区分增强子和沉默子的序列特征，我们在小鼠视网膜中检测了受光感受器 TF cone-rod homeobox (CRX) 靶向的基因组序列的大规模平行报告基因文库。增强子和沉默子都比非活性序列包含更多的 TF 基序，但与沉默子相比，增强子包含来自更多 TF 的基序。我们开发了一种信息含量的度量标准，用于描述序列中基序的数量和多样性，发现虽然增强子和沉默子都依赖于 CRX 基序，但增强子的信息含量更高。信息含量区分由同一 TF 靶向的增强子和沉默子的能力说明了基序上下文如何决定-调控序列的活性。
