PubMed · 8203014
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N A Woychik. 1994. Regulating the regulators.. https://doi.org/10.1016/0968-0004(94)90199-6
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MOTIVATION: Identifying regulatory elements in various chromosomal regions that influence gene expression is a fundamental challenge in epigenomics, with profound implications for understanding gene regulation and disease mechanisms. The advent of paired single-cell RNA sequencing and single-cell ATAC sequencing has created unprecedented opportunities to address this challenge by enabling simultaneous profiling of gene expression and chromatin accessibility at single-cell resolution. However, the inherent signals between them are weak due to the highly sparse and noisy nature of data. RESULTS: This article proposes single-cell meta-Path based Omics Embedding (scPOEM), a novel embedding method that jointly projects chromatin accessibility peaks and expressed genes into a shared low-dimensional space. By integrating the relationships among peak-peak, peak-gene, and gene-gene interactions, scPOEM assigns closer representations in the embedding space to related peak-gene pairs. Our experiments demonstrate that scPOEM generates stable representations of peaks and genes, outperforms existing methods in recovering biologically meaningful peak-gene regulatory relationships and enables new insights in subgroup and differential analysis of gene regulation. These results highlight its potential to uncover gene regulatory mechanisms and enhance the understanding of transcriptional regulation at single-cell resolution. AVAILABILITY AND IMPLEMENTATION: The source code of scPOEM is available at https://github.com/Houyt23/scPOEM. The datasets can be obtained from the 10× Genomics (https://www.10xgenomics.com/datasets/pbmc-from-a-healthy-donor-granulocytes-removed-through-cell-sorting-10-k-1-standard-1-0-0) and GEO database under access codes GSE194122 and GSE239916.
Recent experiments have shown that the previously identified elements in the proximal promoter of IL-4 are not sufficient to fully explain the regulation of its transcription. Consequently we examined another aspect of transcriptional regulation, intergenic transcription, which has been observed throughout the prototypic gene cluster of human beta-globin. These intergenic transcripts are nuclear and it is possible that they play an important functional role in the beta-globin locus. Here we show that intergenic transcription also occurs in the IL-4/IL-13 gene cluster. Intergenic transcription occurs when the surrounding genes are not transcriptionally active; it also occurs in the promoters of these genes; the transcripts are polyadenylated and they remain in the nucleus. We also show that, in HeLa cells which do not express IL-4 or IL-13, intergenic transcription is absent from the region immediately surrounding the genes. This suggests a role for intergenic transcription in the regulation of the IL-4/IL-13 gene cluster.
We describe a modification of the tetracycline-inducible eukaryotic gene expression system with decreased basal levels of expression in HeLa cells. It employs the tetracycline-inducible transactivator and a tetracycline-regulated repressor fusion acting on the same promoter. To avoid heterodimerization or competition for the same DNA site, each was provided with different DNA recognition and/or protein dimerization specificities. We achieved active silencing in the uninduced state resulting in approximately 6-fold reduced levels of basal transcription and several hundred-fold activation of gene expression upon addition of tetracycline.