scholarly journals Long-range telomere regulation of gene expression: Telomere looping and telomere position effect over long distances (TPE-OLD)

2018 ◽  
Vol 99 ◽  
pp. 1-9 ◽  
Author(s):  
Wanil Kim ◽  
Jerry W. Shay
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Position Effect ◽  
Regulation Of Gene Expression ◽  
Telomere Position Effect ◽  
Telomere Regulation

scholarly journals Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances

2014 ◽  
Vol 28 (22) ◽  
pp. 2464-2476 ◽  
Author(s):  
Jérôme D. Robin ◽  
Andrew T. Ludlow ◽  
Kimberly Batten ◽  
Frédérique Magdinier ◽  
Guido Stadler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Position Effect ◽  
Regulation Of Gene Expression ◽  
Telomere Shortening ◽  
Telomere Position Effect

scholarly journals Graph-based data integration predicts long-range regulatory interactions across the human genome

2014 ◽  
Author(s):  
Sofie Demeyer ◽  
Tom Michoel
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Exon Array ◽  
Regulatory Elements ◽  
Computational Method ◽  
Open Chromatin ◽  
Transcription Start Sites ◽  
Distal Regulatory Elements

Transcriptional regulation of gene expression is one of the main processes that affect cell diversification from a single set of genes. Regulatory proteins often interact with DNA regions located distally from the transcription start sites (TSS) of the genes. We developed a computational method that combines open chromatin and gene expression information for a large number of cell types to identify these distal regulatory elements. Our method builds correlation graphs for publicly available DNase-seq and exon array datasets with matching samples and uses graph-based methods to filter findings supported by multiple datasets and remove indirect interactions. The resulting set of interactions was validated with both anecdotal information of known long-range interactions and unbiased experimental data deduced from Hi-C and CAGE experiments. Our results provide a novel set of high-confidence candidate open chromatin regions involved in gene regulation, often located several Mb away from the TSS of their target gene.

scholarly journals Regulation of Gene Expression by Telomere Position Effect

2021 ◽  
Vol 22 (23) ◽  
pp. 12807
Author(s):  
Kyung-Ha Lee ◽  
Do-Yeon Kim ◽  
Wanil Kim
Keyword(s):  
Gene Expression ◽  
Structural Changes ◽  
Genome Rearrangement ◽  
Malignant Tumors ◽  
Human Life ◽  
Position Effect ◽  
Regulation Of Gene Expression ◽  
The Elderly ◽  
Cellular Aging ◽  
Telomere Shortening

Many diseases that involve malignant tumors in the elderly affect the quality of human life; therefore, the relationship between aging and pathogenesis in geriatric diseases must be under-stood to develop appropriate treatments for these diseases. Recent reports have shown that epigenetic regulation caused by changes in the local chromatin structure plays an essential role in aging. This review provides an overview of the roles of telomere shortening on genomic structural changes during an age-dependent shift in gene expression. Telomere shortening is one of the most prominent events that is involved in cellular aging and it affects global gene expression through genome rearrangement. This review provides novel insights into the roles of telomere shortening in disease-affected cells during pathogenesis and suggests novel therapeutic approaches.

scholarly journals Sox2-RNA mechanisms of chromosome topological control in developing forebrain

2020 ◽  
Author(s):  
Ivelisse Cajigas ◽  
Abhijit Chakraborty ◽  
Madison Lynam ◽  
Kelsey R Swyter ◽  
Monique Bastidas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Interaction Sites ◽  
Non Coding Rna ◽  
Selective Targeting ◽  
Chromosome Topology ◽  
Key Sites ◽  
Long Non Coding Rna

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.

scholarly journals Histone H3 Lysine 4 methyltransferases MLL3 and MLL4 Modulate Long-range Chromatin Interactions at Enhancers

2017 ◽  
Author(s):  
Jian Yan ◽  
Shi-An A Chen ◽  
Andrea Local ◽  
Tristin Liu ◽  
Yunjiang Qiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Mammalian Cells ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Active Role ◽  
Specific Gene ◽  
Chromatin Interactions

SUMMARYRegulation of gene expression in mammalian cells depends on long-range chromatin interactions between enhancers and promoters. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here we show that the histone H3 Lysine 4 monomethylation (H3K4me1) writer proteins MLL3 and MLL4 (MLL3/4) play an active role in this process. We demonstrate that in differentiating mouse embryonic stem cells, MLL3/4-dependent deposition of H3K4me1 at enhancers correlates with increased levels of chromatin interactions, whereas loss of MLL3/4 leads to greatly reduced frequencies of chromatin interactions and failure of lineage-specific gene expression programs. We further show that H3K4me1 facilitates recruitment of the Cohesin complex to chromatin in vitro and in vivo, providing a potential mechanism for MLL3/4 to promote chromatin looping. Taken together, our results support an active role for MLL3/4 in modulating chromatin organization at enhancers in mammalian cells.

scholarly journals Imaging assay to probe the role of telomere length shortening on telomere-gene interactions in single cells

Chromosoma ◽  
2021 ◽  
Vol 130 (1) ◽  
pp. 61-73
Author(s):  
Ning Zhang ◽  
Yanhui Li ◽  
Tsung-Po Lai ◽  
Jerry W. Shay ◽  
Gaudenz Danuser
Keyword(s):  
Gene Expression ◽  
Telomere Length ◽  
Single Cells ◽  
Position Effect ◽  
Regulation Of Gene Expression ◽  
Telomeric Sequence ◽  
Long Distance ◽  
Position Effects ◽  
Age Progression

AbstractTelomeres are repetitive non-coding nucleotide sequences (TTAGGGn) capping the ends of chromosomes. Progressive telomere shortening with increasing age has been associated with shifts in gene expression through models such as the telomere position effect (TPE), which suggests reduced interference of the telomere with transcriptional activity of increasingly more distant genes. A modification of the TPE model, referred to as Telomere Position Effects over Long Distance (TPE-OLD), explains why some genes 1–10 MB from a telomere are still affected by TPE, but genes closer to the telomere are not. Here, we describe an imaging approach to systematically examine the occurrence of TPE-OLD at the single cell level. Compared to existing methods, the pipeline allows rapid analysis of hundreds to thousands of cells, which is necessary to establish TPE-OLD as an acceptable mechanism of gene expression regulation. We examined two human genes, ISG15 and TERT, for which TPE-OLD has been described before. For both genes, we found less interaction with the telomere on the same chromosome in old cells compared to young cells; and experimentally elongated telomeres in old cells rescued the level of telomere interaction for both genes. However, the dependency of the interactions on the age progression from young to old cells varied. One model for the differences between ISG15 and TERT may relate to the markedly distinct interstitial telomeric sequence arrangement in the two genes. Overall, this provides a strong rationale for the role of telomere length shortening in the regulation of gene expression.

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

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