A genome-wide CRISPR activation screen identifies SCREEM a novel SNAI1 super-enhancer demarcated by eRNAs.
A genome-wide CRISPR activation screen identifies SCREEM a novel SNAI1 super-enhancer demarcated by eRNAs.
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DOI：
10.3389/fmolb.2023.1110445
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
基因组普遍转录产生大量的非编码rna （ncRNAs）。长链非编码rna （lncRNAs）是bbbb200个核苷酸的转录本，以其调节基因表达的能力而闻名。增强子rna （Enhancer RNAs, eRNAs）是由增强子区域合成的lncrna的一个亚类，也被证明可以协调基因表达。大多数lncrna和erna的生物学功能和意义仍有待确定。上皮向间充质转化（Epithelial to mesenchymal transition， EMT）是一个普遍存在的细胞过程，发生在细胞迁移、体内平衡、纤维化和癌细胞转移过程中。EMT转录因子，如SNAI1诱导复杂的转录程序，协调与EMT相关的形态和分子变化。这种复杂的转录程序通常受到ncRNA网络的协调，因此可以用来鉴定新的功能性ncRNA位点。在这里，使用针对约10,000个lncRNA位点的全基因组CRISPR激活（CRISPRa）筛选，我们确定了可以促进或减弱EMT的ncRNA位点。我们发现了一个新的位点，我们将其命名为SCREEM （SNAI1在单核细胞中表达的顺式调节性erna）。SCREEM位点包含一簇erna，当使用CRISPRa激活时，会诱导邻近基因SNAI1的表达，从而驱动伴随的EMT。然而，SCREEM eRNA转录本本身对于诱导SNAI1表达似乎是不可或缺的。有趣的是，SCREEM erna和SNAI1在活化的单核细胞中共表达，其中SCREEM位点划分了单核细胞特异性超增强子。这些发现提示SNAI1在单核细胞中的潜在作用。对SCREEM-SNAI轴的探索可以揭示单核细胞生物学的新方面。
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.
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识别和功能表征组织特异性和普遍表达的人类 lncRNA。
影响因子：
--
作者：
Jiang C;Li Y;Zhao Z;Lu J;Chen H;Ding N;Wang G;Xu J;Li X
通讯作者：
Li X
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
--
作者：
Jin, Chuan;Yan, Bingchuan;Ma, Lei
通讯作者：
Ma, Lei
影响因子：
3.7
作者：
Bausch-Fluck D;Hofmann A;Bock T;Frei AP;Cerciello F;Jacobs A;Moest H;Omasits U;Gundry RL;Yoon C;Schiess R;Schmidt A;Mirkowska P;Härtlová A;Van Eyk JE;Bourquin JP;Aebersold R;Boheler KR;Zandstra P;Wollscheid B
通讯作者：
Wollscheid B
影响因子：
50.3
作者：
Chen H;Liang H
通讯作者：
Liang H