Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression

Published: March 13, 2025

Mammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another direct of base-unpairing regions (BURs), which genomic elements with high unwinding propensities. Published ChIP-seq datasets show highly accessible at enhancers CTCF sites, but not BURs. By employing urea ChIP-seq, retains only directly bound protein:DNA complexes, we found BURs, targets. SATB1-bound BUR interactions can cross multiple topologically associated domains (TADs) is required for these megabase-scale linked gene expression. BURs mainly within lamina (LADs) sequestered lamina, also in inter-LADs, binds a subset depending on type. Notably, despite mutually exclusive SATB1-binding profiles two methods, most peaks both real require SATB1. Together, propose has functionally distinct modes interaction form scaffold it indirectly tethers open chromatin. Such may provide gene-regulatory network underlying

Language: Английский

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Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression

Published: March 13, 2025

Mammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another direct of base-unpairing regions (BURs), which genomic elements with high unwinding propensities. Published ChIP-seq datasets show highly accessible at enhancers CTCF sites, but not BURs. By employing urea ChIP-seq, retains only directly bound protein:DNA complexes, we found BURs, targets. SATB1-bound BUR interactions can cross multiple topologically associated domains (TADs) is required for these megabase-scale linked gene expression. BURs mainly within lamina (LADs) sequestered lamina, also in inter-LADs, binds a subset depending on type. Notably, despite mutually exclusive SATB1-binding profiles two methods, most peaks both real require SATB1. Together, propose has functionally distinct modes interaction form scaffold it indirectly tethers open chromatin. Such may provide gene-regulatory network underlying

Language: Английский

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Motorized chain models of the ideal chromosome

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(28)

Published: July 2, 2024

An array of motor proteins consumes chemical energy in setting up the architectures chromosomes. Here, we explore how structure ideal polymer chains is influenced by two classes motors. The first class which call "swimming motors" acts to propel chromatin fiber through three-dimensional space. They represent a caricature motors such as RNA polymerases. Previously, they have often been described adding persistent flow onto Brownian diffusion chain. second motors, "grappling caricatures loop extrusion processes segments fibers some distance apart are brought together. We analyze these models using self-consistent variational phonon approximation many-body Master equation incorporating activities. show that whether swimming lead contraction or expansion depends on susceptibility is, their activity forces must exert. Grappling contrast long-ranged correlations resemble those suggested for fractal globules and consistent with effective interactions inferred landscape analyses Hi-C data interphase chromosome.

Language: Английский

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Su(Hw) interacts with Combgap to establish long-range chromatin contacts

Epigenetics & Chromatin, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 21, 2024

Abstract Background Insulator-binding proteins (IBPs) play a critical role in genome architecture by forming and maintaining contact domains. While the involvement of several IBPs organising chromatin Drosophila has been described, specific contribution Suppressor Hairy wings (Su(Hw)) insulator-binding protein to topology remains unclear. Results In this study, we provide evidence for existence long-range interactions between bound Su(Hw) Combgap, which was first characterised as Polycomb response elements binding protein. Loss results disappearance Su(Hw)-Combgap decrease spatial self-interactions among subset Su(Hw)-bound sites. Our findings suggest that are associated with active rather than Polycomb-directed repression. Furthermore, observe majority transcription start sites down-regulated upon loss located within 2 kb Combgap peaks exhibit Su(Hw)-dependent changes transcriptional regulators’ binding. Conclusions This study demonstrates insulator can form protein, these factors dependent

Language: Английский

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Heterogeneity induced Block Copolymer Segregation in Confinement

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Motivated by the work on block copolymer models that provide insights into epigenetics driven chromosome organization, we investigate segregation behavior of five distinct 2-block co-polymers (BCPs) system with varying sizes, confined within both symmetric and lateral geometries. Using exact enumeration method Langevin dynamics simulation, our simple self-avoiding polymer model reveals robust behaviors (across statics dynamic studies) despite strong finite-size effects. We observe as length increases, compaction intensifies relying non-specific interaction, leading to longer times. The study clearly demonstrates formation globular lamellar phases condensed, stable complex structures in long-range (BCP) systems, providing a simplified analogy lamellar-mediated chromatin compaction, which involves are difficult segregate under physiological conditions. Dominance specific interaction over long range BCP systems leads phase separation self assemblies provides heterochromatin—inactive or domains. In contrast, short-range sequences remain coiled state, exhibiting minimal overlap due short attraction, may corresponds euchromatin regions where diverse epigenetic states coexist, resulting active, non-condensed structures. also asymmetric confinement favors more between BCPs irrespective their underlying sequence.

Language: Английский

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Deeply hidden genome organization directly mediated by SATB1

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 21, 2021

Abstract Mammalian genomes are organized by multi-level folding, yet how this organization contributes to cell type-specific transcription remain unclear. We uncovered that the nuclear protein SATB1 establishes two-tiered chromatin organization, one through indirect binding and another direct of base-unpairing regions (BURs), which genomic elements with high unwinding propensities. Published ChIP-seq datasets show highly accessible at enhancers CTCF sites, but not BURs. By employing urea ChIP-seq, retains only directly bound protein:DNA complexes, we found BURs, targets. SATB1-bound BUR interactions can cross multiple topologically associated domains (TADs) is required for these megabase-scale linked gene expression. BURs mainly within lamina (LADs) sequestered lamina, also in inter-LADs, binds a subset depending on type. Notably, despite mutually exclusive SATB1-binding profiles two methods, most peaks both real require SATB1. Together, propose has functionally distinct modes interaction form scaffold it indirectly tethers open chromatin. Such may provide gene-regulatory network underlying

Language: Английский

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