Towards a predictive model of chromatin 3D organization

Xu, Chenhuan; Corcés, Victor G.

doi:10.1016/j.semcdb.2015.11.013

Cited by 15 publications

(14 citation statements)

References 67 publications

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“…Furthermore, the recent identification of the same diverging arrangement in a highly conserved TAD border that predates the origin of deuterostomes suggests that the crucial importance of CTCF orientation is probably an ancestral genomic feature . However, it is important to note that, in the case of flies, no clear association between looping and TAD borders with CTCF binding site orientation has been identified so far . Furthermore, in the highly compacted Drosophila genome, TADs are much smaller than in mammals (60 kb mean size vs 800 kb) .…”

Section: Evidence Of Widespread Tad Organization Across Bilateriansmentioning

confidence: 99%

“…And yet, these species have retained many ancestral microsyntenic pairs, way more than C. elegans . Thus, CTCF could have also been secondarily lost several times in non‐bilaterian lineages, but maintaining long‐range CREs by other means (i.e., evolving novel lineage‐specific architectural proteins such as the ones present in Drosophila ) . However, this seems rather unlikely, suggesting that long‐range regulation could have evolved prior to the origin of bilaterians, in the last common animal ancestor, but that initially these distant chromatin interactions depended on alternative mechanisms or architectural proteins different from CTCF.…”

Section: Evidence Of Widespread Tad Organization Across Bilateriansmentioning

confidence: 99%

“…30 However, it is important to note that, in the case of flies, no clear association between looping and TAD borders with CTCF binding site orientation has been identified so far. 51 Furthermore, in the highly compacted Drosophila genome, TADs are much smaller than in mammals (60 kb mean size vs 800 kb). 23 Thus, although the presence of longrange regulatory interactions and TAD-like structures in both flies and deuterostomes are likely indicative of homology, whether self-interacting domains in Drosophila and mammals are truly equivalent is still an open question.…”

Section: Ctcf Architectural Proteins and Long-range Gene Regulationmentioning

confidence: 99%

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Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals

Acemel

Maeso

Gómez-Skármeta

2017

WIREs Developmental Biology

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The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs). The appearance of the architectural protein CTCF in the bilaterian ancestor likely facilitated the origin of this chromatin 3D organization. TADs play a critical role favoring the contact of cis-regulatory elements with their proper target promoters (that often lay within the same TAD) and preventing undesired regulatory interactions with promoters located in neighboring TADs. We propose that TAD may have had a major influence in the history of the evolution of gene regulation. They have contributed to the increment of regulatory complexity in bilaterians by allowing newly evolved cis-regulatory elements to find target promoters in a range of hundreds of kilobases. In addition, they have conditioned the mechanisms of evolution of gene regulation. These mechanisms include the appearance, removal, or relocation of TAD borders. Such architectural changes have been able to wire or unwire promoters with different sets of cis-regulatory elements in a single mutational event. We discuss the contribution of these architectural changes to the generation of critical genomic 3D structures required for new regulatory mechanisms associated to morphological novelties. WIREs Dev Biol 2017, 6:e265. doi: 10.1002/wdev.265 For further resources related to this article, please visit the WIREs website.

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Section: Evidence Of Widespread Tad Organization Across Bilateriansmentioning

confidence: 99%

Section: Evidence Of Widespread Tad Organization Across Bilateriansmentioning

confidence: 99%

Section: Ctcf Architectural Proteins and Long-range Gene Regulationmentioning

confidence: 99%

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Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals

Acemel

Maeso

Gómez-Skármeta

2017

WIREs Developmental Biology

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“…In human and yeast cells, RNA polymerase III-transcribed sequences were also suggested to serve as insulator sequences with similar mechanisms as CTCF binding sequences. [19][20][21][22][23][24][25][26][27][28] Moreover, various protein binding sequences that form chromatin loops by contacting each other and also exhibit insulator activities have been found in various invertebrates. 19,20,[29][30][31][32][33][34] To precisely regulate gene expression, each enhancer associates with promoters only within the same chromatin domain, with each domain divided by insulators.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23][24][25][26][27][28] Moreover, various protein binding sequences that form chromatin loops by contacting each other and also exhibit insulator activities have been found in various invertebrates. 19,20,[29][30][31][32][33][34] To precisely regulate gene expression, each enhancer associates with promoters only within the same chromatin domain, with each domain divided by insulators. To explain the mechanisms underlying such physically nontrivial limitation of enhancer motion, various models of chromatin dynamics and enhancer-promoter interactions such as the tracking model for DNA binding proteins, looping model based on enhancer-promoter random collision or enhancer scanning, and the topological domain model based on enhancer-promoter random collision have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Insulator Activities of Nucleosome-Excluding DNA Sequences Without Bound Chromatin Looping Proteins

Matsushima

Sakamoto

Awazu

2019

Preprint

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Chromosomes consist of various domains with different transcriptional activities separated by chromatin boundary sequences such as insulator sequences. Recent studies suggested that CTCF or other chromatin loop-forming protein binding sequences represented typical insulators. Alternatively, some long nucleosome-excluding DNA sequences were also reported to exhibit insulator activities in yeast and sea urchin chromosomes although specific binding of loop-forming proteins were not expected for them. However, the mechanism of the insulator activities of these sequences and the possibilities of similar insulators existing in other organisms remained unclear. In this study, we first constructed and performed simulations of a coarse-grained chromatin model containing nucleosome-rich and nucleosome-excluding DNA regions. We found that a long nucleosome-excluding region between two nucleosome-rich regions could markedly hinder the associations of two neighboring chromatin regions owing to the stronger long-term-averaged rigidity of the nucleosome-excluding region compared to that of nucleosome-rich regions. Subsequent analysis of the genome wide nucleosome positioning, protein binding, and DNA rigidity in human cells revealed that some nucleosome-excluding rigid DNA sequences without bound chromatin looping proteins could exhibit insulator activities, functioning as chromatin boundaries in various regions of human chromosomes.the four nucleotide sequences, 84 we defined the rigidity index of each sequence by averaging the rigidities of four sequential nucleotide series. The maximum, central, and minimum values of the rigidities in this data set were 1.9, 11.9, and 27.2. As the rigidity index of ArsInsC sequence was estimated as 14.7, we focused on sequences with rigidity indices > 15 as NENLIS candidate sequences (NENLISc). Through these procedures, we collected the NENLISc in GM12878 cells. Evaluation of the Insulator Activities of NENLISc in Human Cells.To evaluate the insulator activities (the ability to function as a chromatin domain boundary) of NENLISc, we measured the contact probabilities among loci belonging to the 10 kbp up-and downstream chromatin regions of NENLISc using Hi-C data of GM12878 cells with 1 kbp resolution (GEO: GSE63525). We defined !" ! as the contact probability between the s-th and t-th loci around a NENLISc. Here, s and t were the relative positions from the focused NENLISc given as s, t = -10, -9, … , −2, −1, 1, 2, … ,10 (kbp). We considered the case that Hi-C data provides the contact probability between two loci such that the relative positions from the central locus of the focused NENLISc to the loci are given as s' and t', respectively. Then, !" ! is given by the contact probability between the s'-th and t'-th loci wherein the sign of s' (t') and s (t) are the same and |s'| (|t'|) is smaller than |s| (|t|) and larger than {|s| −1 kbp} ({|t| −1 kbp}). We also measured the contact probabilities between the s-th and t-th loci around 11,000 (5000 from each of 22

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Epigenetic Mechanism in Breast Cancer

Verma

Badve

2016

Molecular Pathology of Breast Cancer

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Towards a predictive model of chromatin 3D organization

Cited by 15 publications

References 67 publications

Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals

Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals

Insulator Activities of Nucleosome-Excluding DNA Sequences Without Bound Chromatin Looping Proteins

Epigenetic Mechanism in Breast Cancer

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