Predicting p53-dependent cell transitions from thermodynamic models DOI
Pankaj Gautam,

Isabella Ciuta,

Vladimir B. Teif

et al.

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 161(13)

Published: Oct. 2, 2024

A cell’s fate involves transitions among its various states, each defined by a distinct gene expression profile governed the topology of regulatory networks, which are affected 3D genome organization. Here, we develop thermodynamic models to determine malignant cell as tumor suppressor p53 signaling network, taking into account long-range chromatin interactions in mean-field approximation. The responds stress selectively triggering one potential transcription programs that influence many layers signaling. These range from phosphorylation modulation DNA binding affinity, phase separation phenomena, and internal connectivity genes. We use minimum free energy system fundamental property biological networks influences connection between network state cell. constructed based on equilibrium thermodynamics. Our modeling shows phosphorylated promoters target genes can have properties first order transition. apply our model cancer lines ranging breast (MCF-7), colon (HCT116), leukemia (K562), with characterized specific determines fate. results clarify relevance these mechanisms suggest they represent flexible designs for switching developmental decisions.

Language: Английский

Liquid condensates: a new barrier to loop extrusion? DOI Creative Commons

Arseniy V. Selivanovskiy,

Maria N. Molodova,

Ekaterina E. Khrameeva

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: Feb. 20, 2025

Liquid–liquid phase separation (LLPS), driven by dynamic, low-affinity multivalent interactions of proteins and RNA, results in the formation macromolecular condensates on chromatin. These structures are likely to provide high local concentrations effector factors responsible for various processes including transcriptional regulation DNA repair. In particular, enhancers, super-enhancers, promoters serve as platforms condensate assembly. current paradigm, enhancer-promoter (EP) interaction could be interpreted a result enhancer- promoter-based contact/fusion. There is increasing evidence that spatial juxtaposition enhancers provided loop extrusion (LE) SMC complexes. Here, we propose may act barriers LE, thereby contributing nuclear contacts between regulatory genomic elements.

Language: Английский

Citations

0
Predicting p53-dependent cell transitions from thermodynamic models DOI
Pankaj Gautam,

Isabella Ciuta,

Vladimir B. Teif

et al.

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 161(13)

Published: Oct. 2, 2024

A cell’s fate involves transitions among its various states, each defined by a distinct gene expression profile governed the topology of regulatory networks, which are affected 3D genome organization. Here, we develop thermodynamic models to determine malignant cell as tumor suppressor p53 signaling network, taking into account long-range chromatin interactions in mean-field approximation. The responds stress selectively triggering one potential transcription programs that influence many layers signaling. These range from phosphorylation modulation DNA binding affinity, phase separation phenomena, and internal connectivity genes. We use minimum free energy system fundamental property biological networks influences connection between network state cell. constructed based on equilibrium thermodynamics. Our modeling shows phosphorylated promoters target genes can have properties first order transition. apply our model cancer lines ranging breast (MCF-7), colon (HCT116), leukemia (K562), with characterized specific determines fate. results clarify relevance these mechanisms suggest they represent flexible designs for switching developmental decisions.

Language: Английский

Citations

0