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Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

ABSTRACT: Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

PROVIDER: PRJNA412035 | ENA |

REPOSITORIES: ENA

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Assessing eRNAs associated with a cytokine-sensing mammary super-enhancer

Project description:Enhancers are transcription factor platforms that also bind RNA polymerase II and generate enhancer RNAs (eRNA). Although eRNAs have been suggested as predictors of enhancer activities and possibly key components facilitating transcription, there is little genetic evidence to support this. We address the biology of eRNAs in vivo and investigate eRNA patterns, expression levels and possible functions within a mammary-specific super-enhancer that is composed of three units with distinct transcriptional capacities. We show that eRNA levels do not correspond with the activities of their respective enhancer units. However, changes in eRNA expression upon deletion of individual enhancer units reflect the change in overall super-enhancer activity. These data provide genetic evidence that eRNA levels are not a reliable readout of individual enhancers, but they predict superenhancer activity in the absence of constituent elements.

2018-06-01 | GSE104206 | GEO

Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis

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Functional analysis of CTCF sites associated with cytokine-sensing mammary-specific enhancers in the complex casein locus

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Lineage-specific and non-specific cytokine-sensing genes respond differentially to the master regulator STAT5

Project description:STAT5, a member of the family of Signal Transducers and Activators of Transcription senses cytokines and controls the biology of cell lineages, including mammary, liver and T cells. Here we show that STAT5 activates lineage-specific and widely expressed genes through different mechanisms. STAT5 preferentially binds to promoter sequences of cytokine-responsive genes expressed across cell types and to putative enhancers of lineage-specific genes. While chromatin accessibility of STAT5-based enhancers was dependent on cytokine exposure, STAT5-responsive promoters of widely expressed target genes were generally constitutively accessible. While the contribution of STAT5 to enhancers is well established, its role on promoters is poorly understood. To address this we focused on Socs2, a widely expressed cytokine-sensing gene. Upon deletion of the STAT5 response elements from the Socs2 promoter, cytokine induction was abrogated, while basal activity remained intact. Our data suggest that promoter-bound STAT5 modulates cytokine responses and enhancer-bound STAT5 is mandatory for gene activation.

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eRNAs and super-enhancer lncRNAs are functional in human prostate cancer

Project description:Prostate cancer (PCa) is one of the most commonly diagnosed cancers in males worldwide. lncRNAs (long non-coding RNAs) play a significant role in the occurrence and development of PCa. eRNAs (enhancer RNA) and SE-lncRNAs (super-enhancer lncRNA) are important elements of lncRNAs, but the role of eRNAs and SE-lncRNAs in PCa remains largely unclear. In this work, we identified 681 eRNAs and 292 SE-lncRNAs that were expressed differentially in PCa using a microarray. We constructed a transcriptional regulation network that eRNA related enhancer and the target genes shared the same TF binding motifs. Further, we investigated whether CTCF played a role in mediating the transcriptional regulation network. eRNAs, especially those that regulate androgen response genes, may be candidates for prognostic biomarkers and therapy targets. Our work provide a new perspective for developing medical treatments and therapies for prostate cancer.

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Cytokine-sensing primary enhancer cluster launches secondary enhancers to activate multi-gene locus

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Project description:Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis [ChIP-Seq]

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Assessing Transcriptome Changes in PDX Glioblastoma cells following treatment with a Super-Enhancer Inhibitor

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