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Identification of topologically associated domains (TADs) in peripheral blood CD34+ cells

ABSTRACT: Identification of topologically associated domains (TADs) in peripheral blood CD34+ cells

PROVIDER: PRJNA780868 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16956220_1.fastq.gz	Fastqsanger.gz
	SRR16956220_2.fastq.gz	Fastqsanger.gz
	SRR16956221_1.fastq.gz	Fastqsanger.gz
	SRR16956221_2.fastq.gz	Fastqsanger.gz
	SRR16956222_1.fastq.gz	Fastqsanger.gz

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Identification of topologically associated domains (TADs) in peripheral blood CD34+ cells

Project description:We performed a Hi-C experiment on CD34+ cells isolated from peripheral blood and identifed topologically associated domains (TADs).

2022-09-16 | GSE188940 | GEO

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Project description:Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes of activated B cells to support the process of antibody affinity maturation but also causes "off-target" mutations in other parts of the genome. We have used sensitive lentiviral SHM reporter vectors and a mutationally active human B cell line to identify dozens of regions of the genome that are intrinsically susceptible to SHM ("hot" regions) and many hundreds of regions that are resistant to SHM ("cold" regions). Hot and cold regions are frequently contained within topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while overall levels of transcription are equal, hot TADs are enriched for NIPBL (a component of the cohesin loader), super enhancers, markers of paused/stalled RNA polymerase 2, and multiple transcription factors implicated in B cell development and targeting of SHM. We demonstrate that at least some hot TADs contain enhancer elements that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.

2019-12-04 | GSE139810 | GEO

Pathogenicity of genomic duplications is determined by formation of novel chromatin domains (neo-TADs) (RNA-seq)

Project description:Genome-scale methods have identified subchromosomal structures so-called topologically associated domains (TADs) that subdivide the genome into discrete regulatory units, establish with their target genes. By re-engineering human duplications at the SOX9 locus in mice combined with 4C-seq and Capture Hi-C experiments, we show that genomic duplications can result in the formation of novel chromatin domains (neo-TADs) and that this process determines their molecular pathology.

2016-10-06 | GSE78105 | GEO

Pathogenicity of genomic duplications is determined by formation of novel chromatin domains (neo-TADs) [Hi-C]

2016-10-06 | GSE78072 | GEO

Pathogenicity of genomic duplications is determined by formation of novel chromatin domains (neo-TADs) (4C-seq)

2016-10-06 | GSE78067 | GEO

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Project description:Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

| PRJNA587064 | ENA

Glucocorticoid stimulation induces regionalized gene responses within topologically associating domains

Project description:Glucocorticoid stimulation induces regionalized gene responses within topologically associating domains

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KSHV Topologically Associating Domains in Latent Chromatin and Regulation of Reactivation

Project description:Eukaryotic genomes are structurally organized via the formation of multiple loops that create gene expression regulatory units called topologically associating domains (TADs). Here we revealed the KSHV TAD structure at 500 base pair resolution and constructed a 3D KSHV genomic structural model. The latent KSHV genome formed very similar TAD structures among three different naturally infected PEL cell lines. When KSHV reactivation was triggered, genomic loops within TADs were dramatically decreased, while contacts extending outside of TAD borders increased, leading to formation of a larger regulatory unit with a shift from repressive to active compartments (B to A). The 3D structural model proposes that the immediate-early promoter region is localized on the periphery of the 3D viral genome, while highly inducible non-coding RNA regions moved toward the inner space of the structure, resembling the coordination of a "bird cage" during reactivation. Finally, inhibition of the initial burst of lytic gene expression by stop codon insertion in the viral transactivator reduced genomic loops, while supplementing K-Rta expression in trans during establishment of latency attenuated the defect. Our studies suggest that the latent 3D genomic structural information is embedded in the lytic gene transcription program.

2022-06-25 | GSE163696 | GEO

Active chromatin and transcription play a key role in chromosome partitioning into topologiÑ?ally associating domains

Project description:Recent advances enabled by Hi-C technique have unraveled principles of chromosomal folding, which were since linked to many genomic processes. In particular, Hi-C revealed that chromosomes of animals are organized into Topologically Associating Domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. However, mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principals of TAD folding in Drosophila melanogaster, we performed Hi-C and PolyA+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e. the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predict TAD boundaries much worse than the active chromatin marks (in the minimal case, H3K4me3 and total RNA) do. Moreover, inter-TADs correspond to decompacted interbands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin that cannot be organized into compact structures, possibly due to high levels of histone acetylation. Finally, we test this hypothesis by polymer simulations, and find that TAD partitioning can be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. Hi-C experiments, PolyA+ RNA profiling and mapping of chromosomal rearrangements in four Drosophila melanogaster cell lines.

2015-10-26 | E-GEOD-69013 | biostudies-arrayexpress

Glucocorticoid stimulation induces regionalized gene responses within topologically associating domains

Project description:Transcription-factor binding to cis-regulatory regions regulates the gene expression program of a cell, but occupancy is often a poor predictor of the gene response. Here, we show that glucocorticoid stimulation led to the reorganization of transcriptional coregulators MED1 and BRD4 within topologically associating domains (TADs), resulting in active or repressive gene environments. Indeed, we observed a bias toward the activation or repression of a TAD when their activities were defined by the number of regions gaining and losing MED1 and BRD4 following dexamethasone (Dex) stimulation. Variations in Dex-responsive genes at the RNA levels were consistent with the redistribution of MED1 and BRD4 at the associated cis-regulatory regions. Interestingly, Dex-responsive genes without the differential recruitment of MED1 and BRD4 or binding by the glucocorticoid receptor were found within TADs, which gained or lost MED1 and BRD4, suggesting a role of the surrounding environment in gene regulation. However, the amplitude of the response of Dex-regulated genes was higher when the differential recruitment of the glucocorticoid receptor and transcriptional coregulators was observed, reaffirming the role of transcription factor-driven gene regulation and attributing a lesser role to the TAD environment. These results support a model where a signal-induced transcription factor induces a regionalized effect throughout the TAD, redefining the notion of direct and indirect effects of transcription factors on target genes.

2023-07-19 | GSE226487 | GEO

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