The Experts below are selected from a list of 57159 Experts worldwide ranked by ideXlab platform
Bradley E Bernstein - One of the best experts on this subject based on the ideXlab platform.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed ‘topologically-associated domains’ (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence. The role of CTCF-bound insulator elements in enhancer-gene interactions and transcriptional regulation remains poorly understood. Here, the authors investigate multiple epigenome editing strategies for perturbing individual CTCF-bound Insulators, and evaluate their effects on genome topology and transcription.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed 'topologically-associated domains' (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence.
Daniel R Tarjan - One of the best experts on this subject based on the ideXlab platform.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed ‘topologically-associated domains’ (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence. The role of CTCF-bound insulator elements in enhancer-gene interactions and transcriptional regulation remains poorly understood. Here, the authors investigate multiple epigenome editing strategies for perturbing individual CTCF-bound Insulators, and evaluate their effects on genome topology and transcription.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed 'topologically-associated domains' (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence.
Motohiko Ezawa - One of the best experts on this subject based on the ideXlab platform.
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higher order topological Insulators and semimetals on the breathing kagome and pyrochlore lattices
Physical Review Letters, 2018Co-Authors: Motohiko EzawaAbstract:: A second-order topological insulator in d dimensions is an insulator which has no d-1 dimensional topological boundary states but has d-2 dimensional topological boundary states. It is an extended notion of the conventional topological insulator. Higher-order topological Insulators have been investigated in square and cubic lattices. In this Letter, we generalize them to breathing kagome and pyrochlore lattices. First, we construct a second-order topological insulator on the breathing Kagome lattice. Three topological boundary states emerge at the corner of the triangle, realizing a 1/3 fractional charge at each corner. Second, we construct a third-order topological insulator on the breathing pyrochlore lattice. Four topological boundary states emerge at the corners of the tetrahedron with a 1/4 fractional charge at each corner. These higher-order topological Insulators are characterized by the quantized polarization, which constitutes the bulk topological index. Finally, we study a second-order topological semimetal by stacking the breathing kagome lattice.
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higher order topological Insulators and semimetals on the breathing kagome and pyrochlore lattices
Physical Review Letters, 2018Co-Authors: Motohiko EzawaAbstract:A second-order topological insulator in $d$ dimensions is an insulator which has no $d\ensuremath{-}1$ dimensional topological boundary states but has $d\ensuremath{-}2$ dimensional topological boundary states. It is an extended notion of the conventional topological insulator. Higher-order topological Insulators have been investigated in square and cubic lattices. In this Letter, we generalize them to breathing kagome and pyrochlore lattices. First, we construct a second-order topological insulator on the breathing Kagome lattice. Three topological boundary states emerge at the corner of the triangle, realizing a $1/3$ fractional charge at each corner. Second, we construct a third-order topological insulator on the breathing pyrochlore lattice. Four topological boundary states emerge at the corners of the tetrahedron with a $1/4$ fractional charge at each corner. These higher-order topological Insulators are characterized by the quantized polarization, which constitutes the bulk topological index. Finally, we study a second-order topological semimetal by stacking the breathing kagome lattice.
William A Flavahan - One of the best experts on this subject based on the ideXlab platform.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed ‘topologically-associated domains’ (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence. The role of CTCF-bound insulator elements in enhancer-gene interactions and transcriptional regulation remains poorly understood. Here, the authors investigate multiple epigenome editing strategies for perturbing individual CTCF-bound Insulators, and evaluate their effects on genome topology and transcription.
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epigenome editing strategies for the functional annotation of ctcf Insulators
Nature Communications, 2019Co-Authors: Daniel R Tarjan, William A Flavahan, Bradley E BernsteinAbstract:The human genome is folded into regulatory units termed 'topologically-associated domains' (TADs). Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries. However, the impact of individual Insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF Insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific Insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, partially-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing. Finally, we apply these strategies to simulate an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence.
Baile Zhang - One of the best experts on this subject based on the ideXlab platform.
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acoustic higher order topological insulator on a kagome lattice
Nature Materials, 2019Co-Authors: Haoran Xue, Yahui Yang, Fei Gao, Yidong Chong, Baile ZhangAbstract:Higher-order topological Insulators1-5 are a family of recently predicted topological phases of matter that obey an extended topological bulk-boundary correspondence principle. For example, a two-dimensional (2D) second-order topological insulator does not exhibit gapless one-dimensional (1D) topological edge states, like a standard 2D topological insulator, but instead has topologically protected zero-dimensional (0D) corner states. The first prediction of a second-order topological insulator1, based on quantized quadrupole polarization, was demonstrated in classical mechanical6 and electromagnetic7,8 metamaterials. Here we experimentally realize a second-order topological insulator in an acoustic metamaterial, based on a 'breathing' kagome lattice9 that has zero quadrupole polarization but a non-trivial bulk topology characterized by quantized Wannier centres2,9,10. Unlike previous higher-order topological insulator realizations, the corner states depend not only on the bulk topology but also on the corner shape; we show experimentally that they exist at acute-angled corners of the kagome lattice, but not at obtuse-angled corners. This shape dependence allows corner states to act as topologically protected but reconfigurable local resonances.
