scholarly journals Co-opted transposons help perpetuate conserved higher-order chromosomal structures

2018 ◽  
Author(s):  
Mayank NK Choudhary ◽  
Ryan Z Friedman ◽  
Julia T Wang ◽  
Hyo Sik Jang ◽  
Xiaoyu Zhuo ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Genome Architecture ◽  
3D Genome ◽  
Domain Structures ◽  
Architectural Proteins ◽  
Mammalian Genomes ◽  
Species Specific

ABSTRACTTransposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include architectural proteins—such as CTCF, RAD21 and SMC3—that are involved in tethering chromatin loops and marking domain boundaries. The 3D organization of the mammalian genome is intimately linked to its function and is remarkably conserved. However, the mechanisms by which these structural intricacies emerge and evolve have not been thoroughly probed. Here we show that TEs contribute extensively to both the formation of species-specific loops in humans and mice via deposition of novel anchoring motifs, as well as to the maintenance of conserved loops across both species via CTCF binding site turnover. The latter function demonstrates the ability of TEs to contribute to genome plasticity and reinforce conserved genome architecture as redundant loop anchors. Deleting such candidate TEs in human cells leads to a collapse of such conserved loop and domain structures. These TEs are also marked by reduced DNA methylation and bear mutational signatures of hypomethylation through evolutionary time. TEs have long been considered a source of genetic innovation; by examining their contribution to genome topology, we show that TEs can contribute to regulatory plasticity by inducing redundancy and potentiating genetic drift locally while conserving genome architecture globally, revealing a paradigm for defining regulatory conservation in the noncoding genome beyond classic sequence-level conservation.One-sentence summaryCo-option of transposable elements maintains conserved 3D genome structures via CTCF binding site turnover in human and mouse.

scholarly journals Co-opted transposons help perpetuate conserved higher-order chromosomal structures

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mayank NK Choudhary ◽  
Ryan Z. Friedman ◽  
Julia T. Wang ◽  
Hyo Sik Jang ◽  
Xiaoyu Zhuo ◽  
...  
Keyword(s):  
Binding Sites ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Genome Architecture ◽  
Mutational Signatures ◽  
Domain Structures ◽  
Domain Boundaries ◽  
Architectural Proteins ◽  
Mammalian Genomes ◽  
Species Specific

Abstract Background Transposable elements (TEs) make up half of mammalian genomes and shape genome regulation by harboring binding sites for regulatory factors. These include binding sites for architectural proteins, such as CTCF, RAD21, and SMC3, that are involved in tethering chromatin loops and marking domain boundaries. The 3D organization of the mammalian genome is intimately linked to its function and is remarkably conserved. However, the mechanisms by which these structural intricacies emerge and evolve have not been thoroughly probed. Results Here, we show that TEs contribute extensively to both the formation of species-specific loops in humans and mice through deposition of novel anchoring motifs, as well as to the maintenance of conserved loops across both species through CTCF binding site turnover. The latter function demonstrates the ability of TEs to contribute to genome plasticity and reinforce conserved genome architecture as redundant loop anchors. Deleting such candidate TEs in human cells leads to the collapse of conserved loop and domain structures. These TEs are also marked by reduced DNA methylation and bear mutational signatures of hypomethylation through evolutionary time. Conclusions TEs have long been considered a source of genetic innovation. By examining their contribution to genome topology, we show that TEs can contribute to regulatory plasticity by inducing redundancy and potentiating genetic drift locally while conserving genome architecture globally, revealing a paradigm for defining regulatory conservation in the noncoding genome beyond classic sequence-level conservation.

scholarly journals Transposable elements strongly contribute to cell-specific and species-specific looping diversity in mammalian genomes

2019 ◽  
Author(s):  
Adam G Diehl ◽  
Ningxin Ouyang ◽  
Alan P Boyle
Keyword(s):  
Transposable Elements ◽  
Large Fraction ◽  
Population Level ◽  
Cell Types ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
3D Genome ◽  
Chromatin Looping ◽  
Mammalian Genomes ◽  
Species Specific

AbstractBackgroundChromatin looping is exceedingly important to gene regulation and a host of other nuclear processes. Many recent insights into 3D chromatin structure across species and cell types have contributed to our understanding of the principles governing chromatin looping. However, 3D genome evolution and how it relates to Mendelian selection remain largely unexplored. CTCF, an insulator protein found at most loop anchors, has been described as the “master weaver” of mammalian genomes, and variations in CTCF occupancy are known to influence looping divergence. A large fraction of mammalian CTCF binding sites fall within transposable elements (TEs) but their contributions to looping variation are unknown. Here we investigated the effect of TE-driven CTCF binding site expansions on chromatin looping in human and mouse.ResultsTEs have broadly contributed to CTCF binding and loop boundary specification, primarily forming variable loops across species and cell types and contributing nearly 1/3 of species-specific and cell-specific loops.ConclusionsOur results demonstrate that TE activity is a major source of looping variability across species and cell types. Thus, TE-mediated CTCF expansions explain a large fraction of population-level looping variation and may play a role in adaptive evolution.

scholarly journals 3'HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression

2021 ◽  
Author(s):  
Pamela Himadewi ◽  
Xue Qing David Wang ◽  
Fan Feng ◽  
Haley Gore ◽  
Yushuai Liu ◽  
...  
Keyword(s):  
Binding Site ◽  
Progenitor Cells ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Distal Enhancer ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem ◽  
Ctcf Site

Mutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named Hereditary Persistence of Fetal Hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3 prime end of the β-globin locus, including a CTCF binding site termed 3'HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3'HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.

scholarly journals Transposable Elements in the Organization and Diversification of the Genome of Aegilops speltoides Tausch (Poaceae, Triticeae)

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Olga Raskina
Keyword(s):  
Transposable Elements ◽  
Mobile Element ◽  
Plant Genome ◽  
Aegilops Speltoides ◽  
Genome Architecture ◽  
Different Types ◽  
In The Wild ◽  
Species Specific ◽  
Current Species

Repetitive DNA—specifically, transposable elements (TEs)—is a prevailing genomic fraction in cereals that underlies extensive genome reshuffling and intraspecific diversification in the wild. Although large amounts of data have been accumulated, the effect of TEs on the genome architecture and functioning is not fully understood. Here, plant genome organization was addressed by means of cloning and sequencing TE fragments of different types, which compose the largest portion of the Aegilops speltoides genome. Individual genotypes were analyzed cytogenetically using the cloned TE fragments as the DNA probes for fluorescence in situ hybridization (FISH). The obtained TE sequences of the Ty1-copia, Ty3-gypsy, LINE, and CACTA superfamilies showed the relatedness of the Ae. speltoides genome to the Triticeae tribe and similarities to evolutionarily distant species. A significant number of clones consisted of intercalated fragments of TEs of various types, in which Fatima (Ty3-gypsy) sequences predominated. At the chromosomal level, different TE clones demonstrated sequence-specific patterning, emphasizing the effect of the TE fraction on the Ae. speltoides genome architecture and intraspecific diversification. Altogether, the obtained data highlight the current species-specific organization and patterning of the mobile element fraction and point to ancient evolutionary events in the genome of Ae. speltoides.

Allele-specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32

2005 ◽  
Vol 13 (8) ◽  
pp. 809-818 ◽  
Author(s):  
Alberto L. Rosa ◽  
Yuan-Qing Wu ◽  
Bernard Kwabi-Addo ◽  
Karen J. Coveler ◽  
V. Reid Sutton ◽  
...  
Keyword(s):  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Allele Specific ◽  
Allele Specific Methylation

scholarly journals CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators

2007 ◽  
Vol 36 (Database) ◽  
pp. D83-D87 ◽  
Author(s):  
L. Bao ◽  
M. Zhou ◽  
Y. Cui
Keyword(s):  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site

scholarly journals HTLV-1 inserts an ectopic CTCF-binding site into the human genome

Retrovirology ◽  
2015 ◽  
Vol 12 (S1) ◽  
Author(s):  
Yorifumi Satou ◽  
Miyazato Paola ◽  
Ko Ishihara ◽  
Asami Fukuda ◽  
Kisato Nosaka ◽  
...  
Keyword(s):  
Binding Site ◽  
Human Genome ◽  
Ctcf Binding ◽  
Ctcf Binding Site

scholarly journals Tandem Directional CTCF Sites Balance Protocadherin Promoter Usage

2019 ◽  
Author(s):  
Qiang Wu ◽  
Ya Guo ◽  
Yujia Lu ◽  
Jingwei Li ◽  
Yonghu Wu ◽  
...  
Keyword(s):  
Single Cells ◽  
Computational Simulation ◽  
Ctcf Binding ◽  
Monoallelic Expression ◽  
3D Genome ◽  
Genome Wide ◽  
A Genome ◽  
Mammalian Genomes ◽  
Wide Scale ◽  
Promoter Usage

ABSTRACTCTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the Pcdhα and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter usage. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.

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