scholarly journals Functional impacts of non-coding RNA processing on enhancer activity and target gene expression

2019 ◽  
Vol 11 (10) ◽  
pp. 868-879 ◽  
Author(s):  
Evgenia Ntini ◽  
Annalisa Marsico

Abstract Tight regulation of gene expression is orchestrated by enhancers. Through recent research advancements, it is becoming clear that enhancers are not solely distal regulatory elements harboring transcription factor binding sites and decorated with specific histone marks, but they rather display signatures of active transcription, showing distinct degrees of transcription unit organization. Thereby, a substantial fraction of enhancers give rise to different species of non-coding RNA transcripts with an unprecedented range of potential functions. In this review, we bring together data from recent studies indicating that non-coding RNA transcription from active enhancers, as well as enhancer-produced long non-coding RNA transcripts, may modulate or define the functional regulatory potential of the cognate enhancer. In addition, we summarize supporting evidence that RNA processing of the enhancer-associated long non-coding RNA transcripts may constitute an additional layer of regulation of enhancer activity, which contributes to the control and final outcome of enhancer-targeted gene expression.

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingshui Wang ◽  
Youyu Lin ◽  
Wenting Zhong ◽  
Yu Jiang ◽  
Yao Lin

The death associated protein kinases (DAPKs) are a family of calcium dependent serine/threonine kinases initially identified in the regulation of apoptosis. Previous studies showed that DAPK family members, including DAPK1, DAPK2 and DAPK3 play a crucial regulatory role in malignant tumor development, in terms of cell apoptosis, proliferation, invasion and metastasis. Accumulating evidence has demonstrated that non-coding RNAs, including microRNA (miRNA), long non-coding RNA (lncRNA) and circRNA, are involved in the regulation of gene expression and tumorigenesis. Recent studies indicated that non-coding RNAs participate in the regulation of DAPKs. In this review, we summarized the current knowledge of non-coding RNAs, as well as the potential miRNAs, lncRNAs and circRNAs, that are involved in the regulation of DAPKs.


2020 ◽  
Vol 64 (6) ◽  
pp. 931-945 ◽  
Author(s):  
Fuyan Si ◽  
Xiaofeng Cao ◽  
Xianwei Song ◽  
Xian Deng

Abstract Precursor RNAs undergo extensive processing to become mature RNAs. RNA transcripts are subjected to 5′ capping, 3′-end processing, splicing, and modification; they also form dynamic secondary structures during co-transcriptional and post-transcriptional processing. Like coding RNAs, non-coding RNAs (ncRNAs) undergo extensive processing. For example, secondary small interfering RNA (siRNA) transcripts undergo RNA processing, followed by further cleavage to become mature siRNAs. Transcriptome studies have revealed roles for co-transcriptional and post-transcriptional RNA processing in the regulation of gene expression and the coordination of plant development and plant–environment interactions. In this review, we present the latest progress on RNA processing in gene expression and discuss phased siRNAs (phasiRNAs), a kind of germ cell-specific secondary small RNA (sRNA), focusing on their functions in plant development and environmental responses.


2007 ◽  
Vol 28 (2) ◽  
pp. 575-586 ◽  
Author(s):  
Martín Escamilla-Del-Arenal ◽  
Félix Recillas-Targa

ABSTRACT Long-distance regulatory elements and local chromatin structure are critical for proper regulation of gene expression. Here we characterize the chromatin conformation of the chicken α-globin silencer-enhancer elements located 3′ of the domain. We found a characteristic and erythrocyte-specific structure between the previously defined silencer and the enhancer, defined by two nuclease hypersensitive sites, which appear when the enhancer is active during erythroid differentiation. Fine mapping of these sites demonstrates the absence of a positioned nucleosome and the association of GATA-1. Functional analyses of episomal vectors, as well as stably integrated constructs, revealed that GATA-1 plays a major role in defining both the chromatin structure and the enhancer activity. We detected a progressive enrichment of histone acetylation on critical enhancer nuclear factor binding sites, in correlation with the formation of an apparent nucleosome-free region. On the basis of these results, we propose that the local chromatin structure of the chicken α-globin enhancer plays a central role in its capacity to differentially regulate α-globin gene expression during erythroid differentiation and development.


2020 ◽  
Author(s):  
Ivelisse Cajigas ◽  
Abhijit Chakraborty ◽  
Madison Lynam ◽  
Kelsey R Swyter ◽  
Monique Bastidas ◽  
...  

SummaryPrecise regulation of gene expression networks requires the selective targeting of DNA enhancers. The Evf2 long non-coding RNA regulates Dlx5/6 ultraconserved enhancer(UCE) interactions with long-range target genes, controlling gene expression over a 27Mb region in mouse developing forebrain. Here, we show that Evf2 long range gene repression occurs through multi-step mechanisms involving the transcription factor Sox2, a component of the Evf2 ribonucleoprotein complex (RNP). Evf2 directly interacts with Sox2, antagonizing Sox2-dependent Dlx5/6UCE activation. Evf2 regulates Sox2 binding at key sites, including the Dlx5/6eii shadow enhancer and Dlx5/6UCE interaction sites. Evf2 differentially targets RNP-associated Sox2 protein pools (PPs), redirecting Sox2-PPs to one repressed gene at the expense of the other. Co-regulation of Dlx5/6UCEintrachromosomal interactions by Evf2 and Sox2 reveals a role for Sox2 in chromosome topology. We propose that RNA organizes RNPs in a subnuclear domain, regulating both long-range UCE targeting and activity through Sox2-RNP sequestration and recruitment.


2013 ◽  
Vol 29 (7) ◽  
pp. 471
Author(s):  
Xiaoming JIANG ◽  
Yongfu SHAO ◽  
Bingxiu XIAO ◽  
Junming GUO

2016 ◽  
Author(s):  
Abdullah M. Khamis ◽  
Anna V. Lioznova ◽  
Artem V. Artemov ◽  
Vasily Ramensky ◽  
Vladimir B. Bajic ◽  
...  

AbstractDNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.


2020 ◽  
Author(s):  
Zeyang Shen ◽  
Jenhan Tao ◽  
Gregory J. Fonseca ◽  
Christopher K. Glass

AbstractRegulation of gene expression requires the combinatorial binding of sequence-specific transcription factors (TFs) at promoters and enhancers. Single nucleotide polymorphisms (SNPs) and short insertions and deletions (InDels) can influence gene expression by altering the sequences of TF binding sites. Prior studies also showed that alterations in the spacing between TF binding sites can influence promoter and enhancer activity. However, the relative importance of altered TF spacing has not been systematically analyzed in the context of natural genetic variation. Here, we exploit millions of InDels provided by five diverse strains of mice to globally investigate the effects of altered spacing on TF binding and local histone acetylation in macrophages. We find that spacing alterations resulting from InDels are generally well tolerated in comparison to genetic variants that directly alter TF binding sites. These findings have implications for interpretation of non-coding genetic variation and comparative analysis of regulatory elements across species.


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