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Swathi Jayaram

Bio: Swathi Jayaram is an academic researcher from University of Vienna. The author has contributed to research in topics: Enhancer & Super-enhancer. The author has an hindex of 1, co-authored 1 publications receiving 13 citations.

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Journal ArticleDOI
TL;DR: In this paper, the functions and interdependencies of five enhancer elements that together activate Fgf5 expression during exit from naive murine pluripotency were dissected.

36 citations


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TL;DR: In this article, the authors performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing and found that deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes.
Abstract: Enhancers located in introns are abundant and play a major role in the regulation of gene expression in mammalian species. By contrast, the functions of intronic enhancers in plants have largely been unexplored and only a handful of plant intronic enhancers have been reported. We performed a genome-wide prediction of intronic enhancers in Arabidopsis thaliana using open chromatin signatures based on DNase I sequencing. We identified 941 candidate intronic enhancers associated with 806 genes in seedling tissue and 1,271 intronic enhancers associated with 1,069 genes in floral tissue. We validated the function of 15 of 21 (71%) of the predicted intronic enhancers in transgenic assays using a reporter gene. We also created deletion lines of three intronic enhancers associated with two different genes using CRISPR/Cas. Deletion of these enhancers, which span key transcription factor binding sites, did not abolish gene expression but caused varying levels of transcriptional repression of their cognate genes. Remarkably, the transcriptional repression of the deletion lines occurred at specific developmental stages and resulted in distinct phenotypic effects on plant morphology and development. Clearly, these three intronic enhancers are important in fine-tuning tissue- and development-specific expression of their cognate genes.

27 citations

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TL;DR: A review of the mechanisms by which enhancers engage with promoters, including recent findings on the role of cohesin and the Mediator complex, and how this specificity in enhancer-promoter communication is encoded is provided in this article .

23 citations

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TL;DR: In this paper , the authors discuss major layers of regulation that influence how transcriptional outputs are encoded by DNA sequence and cellular context, and propose a mechanistically informed, quantitative model of transcriptional regulation that integrates these multiple regulatory layers.

22 citations

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TL;DR: In this paper, the authors synthesise classic and recent evidence on the regulatory logic of enhancers, including the principles of enhancer organisation, factors that facilitate and delimit enhancer-promoter communication, and the joint effects of multiple enhancers.
Abstract: Transcriptional enhancers play a key role in the initiation and maintenance of gene expression programmes, particularly in metazoa. How these elements control their target genes in the right place and time is one of the most pertinent questions in functional genomics, with wide implications for most areas of biology. Here, we synthesise classic and recent evidence on the regulatory logic of enhancers, including the principles of enhancer organisation, factors that facilitate and delimit enhancer-promoter communication, and the joint effects of multiple enhancers. We show how modern approaches building on classic insights have begun to unravel the complexity of enhancer-promoter relationships, paving the way towards a quantitative understanding of gene control.

16 citations

Journal ArticleDOI
TL;DR: In this paper, an unbiased approach was developed to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, and the authors discovered a general trend where superenhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo.
Abstract: Background Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell types. How super-enhancers are established during cell differentiation remains obscure. Results Here, by developing an unbiased approach to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, we discover a general trend where super-enhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo. The three types of super-enhancers differ further in association patterns in target gene expression, functional enrichment, and 3D chromatin organization, suggesting they may represent distinct structural and functional subtypes. Furthermore, we dissect the enhancer repertoire within temporally hierarchical super-enhancers, and find enhancers that emerge at early and late stages are enriched with distinct transcription factors, suggesting that the temporal order of establishment of elements within super-enhancers may be directed by underlying DNA sequence. CRISPR-mediated deletion of individual enhancers in differentiated cells shows that both the early- and late-emerged enhancers are indispensable for target gene expression, while in undifferentiated cells early enhancers are involved in the regulation of target genes. Conclusions In summary, our analysis highlights the heterogeneity of the super-enhancer population and provides new insights to enhancer functions within super-enhancers.

14 citations