EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
Cell Syst. 2017 Nov 22;5(5):471-484.e4. doi: 10.1016/j.cels.2017.10.003. Epub 2017 Nov 1.
Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes. Genes regulated by pluripotency factors through super-enhancers show high and correlated expression variability, consistent with fluctuations in the pluripotent state. Together, our results provide an integrated view of how core promoters, chromatin, regulation, and pluripotency fluctuations contribute to the variability of gene expression across individual stem cells.
在相同环境下的同基因细胞在基因表达上表现出显著的细胞间差异，这种差异通常被称为“表达噪声”。在这里，我们使用多个单细胞 RNA 测序数据集来识别与小鼠胚胎干细胞中高或低表达噪声相关的特征。这些特征包括基因的核心启动子结构，其中 CpG 岛启动子和 TATA 盒分别与低噪声和高噪声相关。高噪声还与“冲突”的染色质状态相关联，即在活性基因中缺乏与转录相关的组蛋白修饰或存在抑制性组蛋白修饰。通过超级增强子由多能性因子调控的基因表现出高且相关的表达可变性，这与多能状态的波动一致。总之，我们的研究结果提供了一个综合的观点，即核心启动子、染色质、调控和多能性波动如何共同导致单个干细胞中基因表达的可变性。
