基因组广泛转录生成大量非编码RNA（ncRNA）。长非编码RNA（lncRNA）是由200个核苷酸以上的转录本，以其调节基因表达的能力而闻名。增强子RNA（eRNA）是lncRNA的一个子类，它们是从增强子区域合成的，并被显示出协调基因表达。大部分lncRNA和eRNA的生物功能和意义仍需确定。上皮至间充质转变（EMT）是一种普遍的细胞过程，在细胞迁移、稳态、纤维化和癌细胞转移中都会发生。EMT转录因子（例如SNAI1）诱导一个复杂的转录程式，协调与EMT相关的形态和分子变化。这种复杂的转录程序往往受到ncRNA网络的协调，因此可以利用它们来识别新的功能ncRNA位点。在这里，我们使用覆盖约10,000个lncRNA位点的基因组CRISPR激活（CRISPRa）筛选，确定了可以促进或减弱EMT的ncRNA位点。我们发现了一个名为SCREEM（在单核细胞中表达的SNAI1顺式调控eRNA）的新位点。SCREEM位点包含一个eRNA簇，当使用CRISPRa激活它们时，会诱导相邻基因SNAI1的表达，驱动EMT。然而，SCREEM eRNA转录本本身似乎对于诱导SNAI1表达是不必要的。有趣的是，SCREEM eRNA和SNAI1在活化的单核细胞中共同表达，在那里SCREEM位点标记了一个单核细胞特异性的超级增强子。这些发现暗示了SNAI1在单核细胞中的潜在作用。探索SCREEM-SNAI轴可能揭示单核细胞生物学的新方面。版权所有 © 2023 Uthaya Kumar，Yurieva，Grassmann，Kozhaya，McBride，Unutmaz和Williams。

The genome is pervasively transcribed to produce a vast array of non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides and are best known for their ability to regulate gene expression. Enhancer RNAs (eRNAs) are subclass of lncRNAs that are synthesized from enhancer regions and have also been shown to coordinate gene expression. The biological function and significance of most lncRNAs and eRNAs remain to be determined. Epithelial to mesenchymal transition (EMT) is a ubiquitous cellular process that occurs during cellular migration, homeostasis, fibrosis, and cancer-cell metastasis. EMT-transcription factors, such as SNAI1 induce a complex transcriptional program that coordinates the morphological and molecular changes associated with EMT. Such complex transcriptional programs are often subject to coordination by networks of ncRNAs and thus can be leveraged to identify novel functional ncRNA loci. Here, using a genome-wide CRISPR activation (CRISPRa) screen targeting ∼10,000 lncRNA loci we identified ncRNA loci that could either promote or attenuate EMT. We discovered a novel locus that we named SCREEM (SNAI1 cis-regulatory eRNAs expressed in monocytes). The SCREEM locus contained a cluster of eRNAs that when activated using CRISPRa induced expression of the neighboring gene SNAI1, driving concomitant EMT. However, the SCREEM eRNA transcripts themselves appeared dispensable for the induction of SNAI1 expression. Interestingly, the SCREEM eRNAs and SNAI1 were co-expressed in activated monocytes, where the SCREEM locus demarcated a monocyte-specific super-enhancer. These findings suggest a potential role for SNAI1 in monocytes. Exploration of the SCREEM-SNAI axis could reveal novel aspects of monocyte biology.Copyright © 2023 Uthaya Kumar, Yurieva, Grassmann, Kozhaya, McBride, Unutmaz and Williams.