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Topologically associating domains (TADs) are insufficient for the transcription of β-globin gene and sub-TADs are required for this process

ABSTRACT: Topologically associating domains (TADs) are insufficient for the transcription of β-globin gene and sub-TADs are required for this process

PROVIDER: PRJNA1124140 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29423357_1.fastq.gz	Fastqsanger.gz
	SRR29423357_2.fastq.gz	Fastqsanger.gz
	SRR29423358_1.fastq.gz	Fastqsanger.gz
	SRR29423358_2.fastq.gz	Fastqsanger.gz
	SRR29423359_1.fastq.gz	Fastqsanger.gz

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Topologically associating domains (TADs) are insufficient for the transcription of β-globin gene and sub-TADs are required for this process

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Glucocorticoid stimulation induces regionalized gene responses within topologically associating domains

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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).

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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

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.

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KSHV Topologically Associating Domains in Latent Chromatin and Regulation of Reactivation

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Characterisation of the mouse alpha-globin sub-TAD 3' boundary in erythroid cells [RNA-seq]

Project description:Mammalian genomes are subdivided into large (50-2000 kb) regions of chromatin referred to as Topologically Associating Domains (TADs or sub-TADs). Chromatin within an individual TAD contacts itself more frequently than with regions in surrounding TADs thereby directing enhancer-promoter interactions. In many cases, the borders of TADs are defined by convergently orientated boundary elements associated with CCCTC-binding factor (CTCF), which stabilises the cohesin complex on chromatin and prevents its translocation. This delimits chromatin loop extrusion which is thought to underlie the formation of TADs. However, not all CTCF-bound sites act as boundaries and, importantly, not all TADs are flanked by convergent CTCF sites. Here, we examined the CTCF binding sites within a ~70 kb sub-TAD containing the duplicated mouse α-like globin genes and their five enhancers (5’-R1-R2-R3-Rm-R4-α1-α2-3’). The 5’ border of this sub-TAD is defined by a pair of CTCF sites. Surprisingly, we show that deletion of the CTCF binding sites within and downstream of the α-globin locus leaves the sub-TAD largely intact. The predominant 3’ border of the sub-TAD is defined by a steep reduction in contacts: this corresponds to the transcribed α2-globin gene rather than the CTCF sites at the 3’-end of the sub-TAD. Of interest, the almost identical α1- and α2-globin genes interact differently with the enhancers, resulting in preferential expression of the proximal α1-globin gene which behaves as a partial boundary between the enhancers and the distal α2-globin gene. Together, these observations provide direct evidence that actively transcribed genes can behave as boundary elements.

2022-06-01 | GSE153205 | GEO

Characterisation of the mouse alpha-globin sub-TAD 3' boundary in erythroid cells [ATAC-seq]

2022-06-01 | GSE153207 | GEO

Characterisation of the mouse alpha-globin sub-TAD 3' boundary in erythroid cells [ChIP-seq]

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