Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
BMC Med Genomics. 2024 Apr 17;17(Suppl 1):92. doi: 10.1186/s12920-024-01860-4.
Repressor element 1 (RE1) silencing transcription factor (REST) is a transcriptional repressor abundantly expressed in aging human brains. It is known to regulate genes associated with oxidative stress, inflammation, and neurological disorders by binding to a canonical form of sequence motif and its non-canonical variations. Although analysis of genomic sequence motifs is crucial to understand transcriptional regulation by transcription factors (TFs), a comprehensive characterization of various forms of RE1 motifs in human cell lines has not been performed.
Here, we analyzed 23 ENCODE REST ChIP-seq datasets from diverse human cell lines and identified a non-redundant set of 68,975 loci with ChIP-seq peaks. Our systematic characterization of these binding sites revealed that the canonical form of REST binding motif was found primarily in ChIP-seq peaks shared across multiple cell lines, while non-canonical forms of motifs were identified in both cell-line-specific binding sites and those shared across cell lines. Remarkably, we observed a notable prevalence of non-canonical motifs that corresponded to half segments of the canonical motif. Furthermore, our analysis unveiled the presence of cell-line-specific REST binding patterns, as evidenced by the clustering of ChIP-seq experiments according to their respective cell lines. This observation underscores the cell-line specificity of REST binding at certain genomic loci, implying intricate cell-line-specific regulatory mechanisms.
Overall, our study provides a comprehensive characterization of REST binding motifs in human cell lines and genome-wide RE1 motif profiles. These findings contribute to a deeper understanding of REST-mediated transcriptional regulation and highlight the importance of considering cell-line-specific effects in future investigations.
抑制元件 1（RE1）沉默转录因子（REST）是一种在衰老的人类大脑中大量表达的转录抑制剂。它通过与典型序列基序及其非典型变体结合，来调节与氧化应激、炎症和神经紊乱相关的基因。虽然分析基因组序列基序对于理解转录因子（TFs）的转录调控至关重要，但尚未对人类细胞系中的各种形式的 RE1 基序进行全面表征。
在这里，我们分析了来自不同人类细胞系的 23 个 ENCODE REST ChIP-seq 数据集，并鉴定出具有 ChIP-seq 峰的 68975 个非冗余基因座。我们对这些结合位点的系统表征表明，REST 结合基序的典型形式主要存在于多个细胞系共享的 ChIP-seq 峰中，而非典型形式的基序则存在于细胞系特异性结合位点和细胞系共享的结合位点中。值得注意的是，我们观察到非典型基序的明显普遍性，它们对应于典型基序的一半片段。此外，我们的分析揭示了细胞系特异性 REST 结合模式的存在，这表现在根据各自的细胞系对 ChIP-seq 实验进行聚类。这一观察结果强调了 REST 在某些基因组位点的细胞系特异性结合，暗示了复杂的细胞系特异性调节机制。
总体而言，我们的研究提供了人类细胞系中 REST 结合基序和全基因组 RE1 基序图谱的全面表征。这些发现有助于深入了解 REST 介导的转录调控，并强调了在未来研究中考虑细胞系特异性效应的重要性。
