The Transcription Factor ThPOK Orchestrates Stochastic Interchromosomal Interactions Required for IFNB1 Virus-Inducible Gene Expression

Nikopoulou, Chrysa; Panagopoulos, Giorgos; Sianidis, Georgios; Psarra, Eleni; Ford, Ethan; Thanos, Dimitris

doi:10.1016/j.molcel.2019.04.004

Cited by 2 publications

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“…Hence, how does it specifically activate IFNβ expression is questionable? Nikopoulou et al (2019) have a good explanation for this query. They revealed that exogenous or endogenous stimulation induces ThPOK, a transcription factor, to bind to NRC21 on multiple sites, including the conservative GAGA elements that facilitate interchromosomal interaction.…”

Section: Ifnβ Transcription Regulationmentioning

confidence: 94%

Regulation of IFNβ expression: focusing on the role of its promoter and transcription regulators

et al. 2023

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IFNβ is a single-copy gene without an intron. Under normal circumstances, it shows low or no expression in cells. It is upregulated only when the body needs it or is stimulated. Stimuli bind to the pattern recognition receptors (PRRs) and pass via various signaling pathways to several basic transcriptional regulators, such as IRFs, NF-кB, and AP-1. Subsequently, the transcriptional regulators enter the nucleus and bind to regulatory elements of the IFNβ promoter. After various modifications, the position of the nucleosome is altered and the complex is assembled to activate the IFNβ expression. However, IFNβ regulation involves a complex network. For the study of immunity and diseases, it is important to understand how transcription factors bind to regulatory elements through specific forms, which elements in cells are involved in regulation, what regulation occurs during the assembly of enhancers and transcription complexes, and the possible regulatory mechanisms after transcription. Thus, this review focuses on the various regulatory mechanisms and elements involved in the activation of IFNβ expression. In addition, we discuss the impact of this regulation in biology.

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Section: Ifnβ Transcription Regulationmentioning

confidence: 94%

Regulation of IFNβ expression: focusing on the role of its promoter and transcription regulators

et al. 2023

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“…Thus, how the cells can harmonize the entire set of chromosomes within the nuclei remains largely unknown [30][31][32][33][34] . The occurrence of direct inter-chromosomal interactions or trans-acting contacts provides one potential strategy for the coordination of chromatin conformation in response to certain stimuli [35][36][37][38][39][40] . For example, the complex choreography of olfactory receptor genes, which are located across several different chromosomes, involves frequent inter-chromosomal interactions in the form of the "olfactosome" to determine specific olfactory receptor genes' expression in sensory neurons 41,42 .…”

Section: Introductionmentioning

confidence: 99%

Genomic locus of lncRNA-Gm26793forms an inter-chromosomal molecular lock withCubnto ensure proper stem cell differentiation and mouse embryogenesis

Liu,

Yang,

Chen

et al. 2023

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Inter-chromosomal interactions play a crucial role in 3D genome organization, yet the organizational principles and functional significances remain elusive. In general, long non-coding RNA (lncRNA) loci and transcripts are frequently associated with transcriptional programs modulated by long-range chromatin interactions. Here, we identified a novel lncRNA namedGm26793, which is abundantly distributed in the primitive streak and mesodermal cells of E7.5 mouse gastrula. Through genetic ablation ofGm26793, we observed a preferential responsiveness to primitive endoderm lineage during stem cell differentiation, as well as enhanced occurrence of transient and degenerative state cells in early mouse embryos when the cell fate segregates between epiblast and primitive endoderm. Mechanistically, we revealed the genomic locus ofGm26793, rather than the lncRNA transcript or adjacent gene governs the cell fate preference towards primitive endoderm. Concretely,Gm26793locus (Chr 7) forms an inter-chromosomal molecular lock withCubn(Chr 2), restraining the expression ofCubnand maintaining a natural epigenetic landscape, thus ensuring the proper lineage specificationin vitroandin vivo. In order to reinforce this lock, CTCF and cohesin complex serves as a ring to fasten the inter-chromosomal contact. Overall, our study provides a clear paradigm that inter-chromosomal interaction collaborates with architectural factors to stabilize nuclear conformation and guarantee faithful gene expression during stem cell differentiation and mammalian embryogenesis.

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The Transcription Factor ThPOK Orchestrates Stochastic Interchromosomal Interactions Required for IFNB1 Virus-Inducible Gene Expression

Cited by 2 publications

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Regulation of IFNβ expression: focusing on the role of its promoter and transcription regulators

Regulation of IFNβ expression: focusing on the role of its promoter and transcription regulators

Genomic locus of lncRNA-Gm26793forms an inter-chromosomal molecular lock withCubnto ensure proper stem cell differentiation and mouse embryogenesis

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