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Genetic Engineering Publications - GEG Tech top picks
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BigField GEG Tech's insight:
In this study, the scientists used highly efficient targeted chromosomal deletions induced by the CRISPR/Cas9 genome editing tool to characterise two functional enhancers: FOXP2-Eproximal and FOXP2-Edistal, located in the intergenic region between FOXP2 and its adjacent MDFIC gene. Deletion of any of these two functional enhancers in a neuroectodermal tumor cell-line downregulates FOXP2 and decreases FOXP2 protein levels, conversely it upregulates MDFIC and increases MDFIC protein levels. The authors expect these findings contribute to a deeper understanding of FOXP2 and MDFIC may pace the development of speech and language in the brain. 
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A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9 mediated genetic screening
BigField GEG Tech's insight:
Here, the scientists have developed a high throughput CRISPR/Cas9-based genome-editing strategy and used it to interrogate 174 candidate regulatory sequences within the 1Mbp POU5F1 locus in the human embryonic stem cells (hESCs). They identified two classical regulatory elements that are essential for POU5F1 transcription in the hESCs. Unexpectedly, they also discovered a new class of enhancers that contribute to POU5F1 transcription in an unusual way: disruption of such sequences led to a temporary loss of POU5F1 transcription that is fully restored after a few rounds of cell division. These results demonstrate the utility of a high throughput screening for functional characterization of non-coding DNA, and reveal a previously unrecognized layer of gene regulation in human cells.
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BigField GEG Tech's insight:
The authors show that CRISPR-Cas9-mediated ablation of lncRNA-CSR transcription decreases its chromosomal looping-mediated association with the IgH 3′ regulatory region super-enhancer and leads to decreased class switch recombination efficiency. They propose that the RNA exosome protects divergently transcribed lncRNA expressing enhancers by resolving deleterious transcription-coupled secondary DNA structures, while also regulating long-range super-enhancer chromosomal interactions important for cellular function.
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BigField GEG Tech's insight:
Here, the authors demonstrate striking differences in super-enhancer transcriptional regulation of Nanog. In addition, they show that a distal super-enhancer differentially regulates multiple neighboring genes and that eRNAs produced at this super-enhancer selectively activate expression of one neighboring gene. Thus, eRNAs are critical to enhancer function. This study provides insight into the mechanism of transcribed enhancers in a cluster of co-regulated genes, specifically parsing out genes that cluster with a highly active transcribed enhancer versus a subset of genes the enhancer regulates.
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BigField GEG Tech's insight:
Here, the scientists discuss the application, current limitations and future development of CRISPR–Cas9 systems to identify and characterize enhancer elements in a high-throughput manner.
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BigField GEG Tech's insight:
In this study, the authors show that human IDH mutant gliomas exhibit hypermethylation at cohesin and CCCTC-binding factor (CTCF)-binding sites, compromising binding of this methylation-sensitive insulator protein. They used the CRISPR system to disrupt CTCF and observed in IDH wild-type gliomaspheres the upregulation of PDGFRA and the increasing of proliferation
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BigField GEG Tech's insight:
Using CRISPR/Cas9, the scientists developed 32Dcl3 lines in which the wild-type enhancer alleles are replaced with a variant mutant in the seven Ets sites. In this way, the show that the +37 kb Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that impact its expression during normal hematopoiesis and potentially during myeloid transformation.
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In this study, the authors present a high-throughput approach that uses CRISPR interference (CRISPRi) to discover regulatory elements and identify their target genes. They assess >1 megabase (Mb) of sequence in the vicinity of 2 essential transcription factors, MYC and GATA1, and identify 9 distal enhancers that control gene expression and cellular proliferation. This CRISPRi-based approach can be applied to dissect transcriptional networks and interpret the contributions of noncoding genetic variation to human disease.