Novel biological insights revealed from the investigation of multiscale genome architecture

Ding, Tianyi; Zhang, He

doi:10.1016/j.csbj.2022.12.009

Cited by 4 publications

(3 citation statements)

References 177 publications

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“…Chromatin loop is relatively stable, ring‐shaped structure formed by chromatin within 3D space, often containing regulatory elements such as enhancers and promoters. 76 In 2014, Rao and colleagues discovered approximately 10,000 chromatin loops through the analysis of in situ Hi‐C conducted on human lymphoblastoid cells. 15 Most of these loops are conservation across various species and cell types.…”

Section: D Genome Structurementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Section: D Genome Structurementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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“…Despite the fact that employing promoters of varying strengths is one of the most crucial methods for regulating gene expressions, the integration of diverse regulatory elements such as Ribosome Binding Sites (RBS), terminators, insulators, and others, offers expanded options for gene expression modulation (39)(40)(41). Furthermore, synthetic promoters, which establish a predetermined expression intensity, present challenges in dynamically regulating gene expression during growth.…”

Section: Discussionmentioning

confidence: 99%

Species-specific design of artificial promoters by transfer-learning based generative deep-learning model

Xia,

Du,

Liu

et al. 2023

Preprint

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Native prokaryotic promoters share common sequence patterns, but are species dependent. For understudied species with limited data, it is challenging to predict the strength of existing promoters and generate novel promoters. Here, we developed PromoGen, a collection of nucleotide language models to generate species-specific functional promoters, across dozens of species in a data and parameter efficient way. Twenty-seven species-specific models in this collection were finetuned from the pretrained model which was trained on multi-species promoters. When systematically compared with native promoters, theEscherichia coli-andBacillus subtilis-specific artificial PromoGen-generated promoters (PGPs) were demonstrated to hold all essential features and distribution patterns of native promoters. A regression model was developed to score generated either by PromoGen or by another competitive neural network, and the overall score of PGPs is higher. Encouraged byin silicoanalysis, we further experimentally characterized twenty-twoB. subtilisPGPsin vivo, results showed that four of tested PGPs reached the strong promoter level while all were active. Furthermore, we developed a user-friendly website to generate species-specific promoters for 27 different species by PromoGen. This work presented an efficient deep-learning strategy forde novospecies-specific promoter generation even with limited datasets, providing valuable promoter toolboxes especially for the metabolic engineering of understudied microorganisms.Abstract Figure

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“…Cells cultured in a 3D environment are exposed to spatiotemporal cues such as cell-to-cell and cell-to-ECM interactions, which influence signal transduction, gene expression, and cellular behaviour during proliferation and differentiation [1][2][3]. As a result, a large amount of effort has gone into developing 3D cell culture techniques and materials that can replicate tissue-specific features and evaluate drug responses more accurately [6,7]. Along with the development of more physiologically relevant 3D cell culture models, researchers bear the responsibility of validating new cell assay techniques capable of measuring and evaluating constructs that are physically larger and more complex compared to 2D cell cultures [8].…”

Section: Introductionmentioning

confidence: 99%

Flow cytometry as an analytical method of drug-induced apoptosis in 3D bioprinted melanoma cells

Villiers

Plessis

2023

Biomed. Mater.

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Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to its inherent advantages in providing more physiologically relevant information and more predictive data for in vivo tests. Along with the development of more physiologically relevant 3D cell culture models, researchers bear the responsibility to validate new cell assay techniques capable of measuring and evaluating constructs that are physically larger and more complex compared to two- dimensional (2D) cell cultures. It is important to note that assays based on monolayer cultures may be insufficient for the use in 3D cell cultures models. In this study we firstly fabricated a 3D bioprinted hydrogel melanoma scaffold. This was used to validate a flow cytometry-based analytical method as a tool for 3D bioprinted structures to assess drug-induced apoptosis. The results indicated high robustness, reproducibility and sensitivity of the flow cytometric method established on the 3D cell-laden A375 melanoma hydrogel scaffolds. Over and above this, it was possible to determine the effect of etoposide on A375 melanoma cells using Annexin V and PI apoptosis assay.

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Novel biological insights revealed from the investigation of multiscale genome architecture

Cited by 4 publications

References 177 publications

Three‐dimensional genome structure and function

Three‐dimensional genome structure and function

Species-specific design of artificial promoters by transfer-learning based generative deep-learning model

Flow cytometry as an analytical method of drug-induced apoptosis in 3D bioprinted melanoma cells

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