Contribution of Topological Domains and Loop Formation to 3D Chromatin Organization

Ea, Vuthy; Baudement, Marie-Odile; Lesne, Annick; Forné, Thierry

doi:10.3390/genes6030734

Cited by 57 publications

(50 citation statements)

References 59 publications

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“…3). Numerous studies performed in human and murine cultured and primary cell lines have identified CTCF as a key regulator of TAD formation in mammals [4, 52–54]. However, we do not see the loss of TADs or dramatic changes in the TAD profile in differentiated HD3 cells in spite of dramatic loss of CTCF occupancy at the binding sites within the studied area (Fig.…”

Section: Discussioncontrasting

confidence: 59%

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

Ulianov

Galitsyna

Flyamer

et al. 2017

Epigenetics & Chromatin

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BackgroundIn homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation.ResultsWe found that, similarly to mammalian genome, the chicken genomes is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream major regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation.ConclusionsOur findings demonstrate that the effects of tissue-specific transcription activation are not restricted to the host genomic locus but affect the overall chromatin structure and transcriptional output of the encompassing topologically associating domain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-017-0142-4) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 59%

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

Ulianov

Galitsyna

Flyamer

et al. 2017

Epigenetics & Chromatin

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“…Specifically, CTCF has many roles in regulating gene expression as an insulator and in its role in chromatin architecture 24–26 . Data published in ENCODE 27 using multiple cell lines including small airway epithelial cells (SAEC) indicated that CTCF binds to this region 28 , so we tested CTCF binding affinity to the IFITM3 promoter.…”

Section: Resultsmentioning

confidence: 99%

SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans

Allen

Randolph

Bhangale³

et al. 2017

Nat Med

173

220

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Previous studies reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism of risk remains controversial. We prioritized SNPs in IFITM3 based on putative biological function and identified rs34481144 in the 5′ UTR. We found evidence of a novel association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined the role of rs34481144 as an expression quantitative trait loci (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression. The risk allele was found to have decreased IRF3 binding and increased CTCF binding in promoter-binding assays, and risk allele carriage diminished transcriptional correlations among neighboring genes, indicative of CTCF boundary activity. Furthermore, the risk allele disrupts a CpG site that undergoes differential methylation in CD8 T-cell subsets. Carriers of the risk allele had reduced CD8 T-cells in their airways during natural influenza infection, consistent with IFITM3 promoting airway CD8 T-cell accumulation, indicating that a critical function for IFITM3 may be to promote immune cell persistence at mucosal sites. Our study identifies a new regulator of IFITM3 expression that associates with CD8 T-cell levels in the airways and a spectrum of clinical outcomes.

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“…TAD boundaries were found to be enriched in binding sites to proteins CTCF (CCCTC-binding factor) and cohesin, as well as to transcription start sites, histone marks of active chromatin, housekeeping genes, and short interspersed nuclear elements. 45 CTCF is a highly conserved transcription factor that can act as a transcriptional activator, repressor, and insulator; it is involved in many cellular processes, including regulation of chromatin structure. 46 Cohesin is a multisubunit protein, ring-shaped complex composed of four core subunits: two SMC proteins (SMC1 and 3), an alpha-kleisin (Rad21/Scc1), and an orthologue of the yeast Scc3 protein.…”

Section: Tad Related Proteinsmentioning

confidence: 99%

Chromatin dynamics governed by a set of nuclear structural proteins

Vivante

Brozgol

Bronshtein

et al. 2019

Genes Chromosomes & Cancer

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During the past three decades, the study of nuclear and chromatin organization has become of great interest. The organization and dynamics of chromatin are directly responsible for many functions including gene regulation, genome replication, and maintenance. In order to better understand the details of these mechanisms, we need to understand the role of specific proteins that take part in these processes. The genome in the nucleus is organized in different length scales, ranging from the bead‐like nucleosomes through topological associated domains up to chromosome territories. The mechanisms that maintain these structures, however, remain to be fully elucidated. Previous works highlighted the significance of lamin A, an important nucleoplasmic protein; however, there are other nuclear structural proteins that are also important for chromatin organization. Studying the organizational aspects of the nucleus is a complex task, and different methods have been developed and adopted for this purpose, including molecular and imaging methods. Here we describe the use of the live‐cell imaging method and demonstrate that the dynamics of the nucleus is strongly related to its organizational mechanisms. We labeled different genomic sites in the nucleus and measured the effect of nuclear structural proteins on their dynamics. We studied lamin A, BAF, Emerin, lamin B, CTCF, and Cohesin and discuss how each of them affect chromatin dynamics. Our findings indicate that lamin A and BAF have a significant effect on chromosomes dynamics, while other proteins mildly affect the type of the diffusion while the volume of motion is not affected.

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Contribution of Topological Domains and Loop Formation to 3D Chromatin Organization

Cited by 57 publications

References 59 publications

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans

Chromatin dynamics governed by a set of nuclear structural proteins

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