On the role of transcription in positioning nucleosomes

Jiang, Zhongling; Zhang, Bin

doi:10.1101/2020.04.07.029892

Cited by 5 publications

(5 citation statements)

References 69 publications

(76 reference statements)

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“…Additionally, RES-A cells had a higher proportion of unique open sites compared to P < 0.001, and LNCaP (19% vs 7%, P < 0.001, chi-square test) ( Figure 1C ). These findings are consistent with TSS non-targeted opening (Jiang and Zhang, 2021) of the chromatin upon enzalutamide resistance.…”

Section: Chromatin Reprogramming Underpins Enzalutamide Resistancesupporting

confidence: 88%

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Taavitsainen

Engedal

Cao

et al. 2021

Preprint

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Prostate cancer is profoundly heterogeneous and patients would benefit from methods that stratify clinically indolent from more aggressive forms of the disease. We employed single-cell assay for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that high analytical resolution of pre-clinical models may powerfully inform clinical decision-making.

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Section: Chromatin Reprogramming Underpins Enzalutamide Resistancesupporting

confidence: 88%

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Taavitsainen

Engedal

Cao

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…1C). These ndings are consistent with TSS non-targeted opening (Jiang and Zhang, 2021) of the chromatin upon ENZ resistance.…”

Section: Chromatin Reprogramming Underpins Enzalutamide Resistancesupporting

confidence: 86%

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Taavitsainen

Engedal

Cao

et al. 2021

Preprint

View full text Add to dashboard Cite

Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond to systemic therapy. We employed single-cell assays for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that were linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that the high analytical resolution of pre-clinical models enabled by single-cell methods may powerfully inform clinical decision-making.

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“…The ideal potential was specifically designed to account for the role of molecular motors like Cohesin that can compact individual chromosomes. 55,56 Other active processes, including transcription and nucleosome remodeling, 51,53,[68][69][70][71] can also lead to non-conservative forces to perturb chromosome structures. The effect of these processes, together with passive interactions arising from epigenetic modifications and chromatin regulators, may produce the effective compartment specific potential inferred from Hi-C data.…”

Section: Active Forces Drive Peripheral Localization Of Heterochromatinmentioning

confidence: 99%

Phase Separation and Correlated Motions in Motorized Genome

Jiang

Kamat

et al. 2022

Preprint

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The human genome is arranged in the cell nucleus non-randomly, and phase separation has been proposed as an important driving force for genome organization. However, the cell nucleus is an active system, and the contribution of non-equilibrium activities to phase separation and genome structure and dynamics remains to be explored. We simulated the genome using an energy function parameterized with chromosome conformation capture (Hi-C) data with the presence of active, nondirectional forces that break the detailed balance. We found that active forces that may arise from transcription and chromatin remodeling can dramatically impact the spatial localization of heterochromatin. When applied to euchromatin, active forces can drive heterochromatin to the nuclear envelope and compete with passive interactions among heterochromatin that tend to pull them in opposite directions. Furthermore, active forces induce long-range spatial correlations among genomic loci beyond single chromosome territories. We further showed that the impact of active forces could be understood from the effective temperature defined as the fluctuation-dissipation ratio. Our study suggests that non-equilibrium activities can significantly impact genome structure and dynamics, producing unexpected collective phenomena.

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On the role of transcription in positioning nucleosomes

Cited by 5 publications

References 69 publications

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Phase Separation and Correlated Motions in Motorized Genome

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