Deeply hidden genome organization directly mediated by SATB1 DOI Open Access
Yoshinori Kohwi, Xianrong Wong,

Marie-Pierre Grange

et al.

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

SATB2 organizes the 3D genome architecture of cognition in cortical neurons DOI Creative Commons
Nico Wahl, Sergio Espeso‐Gil,

Paola Chietera

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(4), P. 621 - 639.e9

Published: Jan. 21, 2024

The DNA-binding protein SATB2 is genetically linked to human intelligence. We studied its influence on the three-dimensional (3D) epigenome by mapping chromatin interactions and accessibility in control versus SATB2-deficient cortical neurons. find that affects looping between enhancers promoters of neuronal-activity-regulated genes, thus influencing their expression. It also alters A/B compartments, topologically associating domains, frequently interacting regions. Genes SATB2-dependent 3D genome changes are implicated highly specialized neuronal functions contribute cognitive ability risk for neuropsychiatric neurodevelopmental disorders. Non-coding DNA regions with a structure enriched common variants associated educational attainment, intelligence, schizophrenia. Our data establish as cell-type-specific modulator, which operates both independently cooperation CCCTC-binding factor (CTCF) set up landscape pyramidal neurons processes.

Language: Английский

Citations

9
Matrin3 mediates differentiation through stabilizing chromatin loop-domain interactions and YY1 mediated enhancer-promoter interactions DOI Creative Commons
Tianxin Liu, Qian Zhu, Kai Yan

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 10, 2024

Abstract Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate direct role of abundant complex protein Matrin3 (Matr3) chromatin development context myogenesis. Using an acute targeted degradation platform (dTAG-Matr3), reveal dynamics development-related reorganization. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected, accompanied by emergence novel YY1-mediated enhancer-promoter loops, which occurred concurrently with histone modifications chromatin-level patterns. Changes occupancy also correlated these alterations. Overall, our results suggest mediates differentiation through stabilizing accessibility loop-domain interactions, highlight a conserved for maintenance architecture.

Language: Английский

Citations

8
Deciphering the TET3 interactome in primary thymic developing T cells DOI Creative Commons

Dimitris Theofilatos,

Tricia Ho,

Greg Waitt

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109782 - 109782

Published: April 18, 2024

Ten-eleven translocation (TET) proteins are DNA dioxygenases that mediate active demethylation. TET3 is the most highly expressed TET protein in thymic developing T cells. TET3, either independently or cooperation with TET1 TET2, has been implicated cell lineage specification by regulating However, TET-deficient mice exhibit complex phenotypes, suggesting exerts multifaceted roles, potentially interacting other proteins. We performed liquid chromatography tandem mass spectrometry primary cells to identify partners endogenous,

Language: Английский

Citations

6
CircSATB1 Promotes Colorectal Cancer Liver Metastasis through Facilitating FKBP8 Degradation via RNF25‐Mediated Ubiquitination DOI Creative Commons

Chuan Zhang,

Chen Tian,

Renzhong Zhu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Colorectal cancer (CRC) is one of the most common cancers worldwide and liver metastasis leading reason for its mortality. Circular RNAs (circRNAs) are conclusively associated with progression various cancers, rendering exploration specific mechanisms in colorectal metastasis(CRLM) highly valuable. Combined GEO (Gene Expression Omnibus) databases clinical data our center, we found that high expression circSATB1 closely related to CRLM. Functionally, could significantly promote metastatic ability CRC cells vitro vivo. Mechanistically, facilitated RNF25-mediated ubiquitylation degradation FKBP8, releasing inhibitory effects on mTOR signaling. In this process, acted as a scaffold RNF25-FKBP8 complexes. Additionally, be packaged exosomes secreted from primary tumors into plasma. conclusion, study uncovered new acts potent promoter CRLM offers novel insights precision therapeutic strategies

Language: Английский

Citations

0
SATB1 in cancer progression and metastasis: mechanisms and therapeutic potential DOI Creative Commons

Jinping Bai,

Gege Yang,

Qi Yu

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 25, 2025

Cancer remains a major global health challenge, with prostate cancer, lung colorectal and breast cancer accounting for nearly half of all diagnoses. Despite advancements in treatment, metastasis to distant organs continues be the leading cause cancer-related mortality. The progression involves alteration numerous genes, dynamic changes chromatin organization histone modifications playing critical role regulating cancer-associated genes. Special AT-rich sequence-binding protein 1 (SATB1), organizer, plays pivotal by gene expression, remodeling, cell signaling pathways. SATB1 binds DNA sequences, acting as scaffold chromatin-modifying enzymes transcription factors, thus coordinating regulation extensive networks. Its overexpression has been implicated wide range cancers is associated poor prognosis, aggressive tumor phenotypes, enhanced epithelial-mesenchymal transition (EMT). Moreover, SATB1's activity modulated microRNAs (miRNAs) post-translational modifications, further contributing its complex regulatory functions. Given crucial involvement metastasis, emerged promising target novel therapeutic strategies. This review delves into molecular mechanisms explores potential approaches targeting this key regulator treatment.

Language: Английский

Citations

0
Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression DOI Open Access
Yoshinori Kohwi, Xianrong Wong,

Marie-Pierre Grange

et al.

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

Citations

0
Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression DOI Open Access
Yoshinori Kohwi, Xianrong Wong,

Marie-Pierre Grange

et al.

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

Citations

0
Regulation of 3D genome organization during T cell activation DOI Open Access
Bao Wang, Qian Bian

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: June 29, 2024

Within the three-dimensional (3D) nuclear space, genome organizes into a series of orderly structures that impose important influences on gene regulation. T lymphocytes, crucial players in adaptive immune responses, undergo intricate transcriptional remodeling upon activation, leading to differentiation specific effector and memory cell subsets. Recent evidence suggests activation is accompanied by dynamic changes architecture at multiple levels, providing unique biological context explore functional relevance molecular mechanisms 3D organization. Here, we summarize recent advances link reorganization programs conversion fates during differentiation. We further discuss how various chromatin regulators, including CCCTC-binding factor several transcription factors, collectively modulate this process.

Language: Английский

Citations

3
SATB1, senescence and senescence‐related diseases DOI

Wenjing Qi,

Jinping Bai,

Ruoxi Wang

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(8)

Published: May 27, 2024

Abstract Aging leads to an accumulation of cellular mutations and damage, increasing the risk senescence, apoptosis, malignant transformation. Cellular which is pivotal in aging, acts as both a guard against transformation check cancer progression. It marked by stable cell cycle arrest, widespread macromolecular changes, pro‐inflammatory profile, altered gene expression. However, it remains be determined whether these differing subsets senescent cells result from unique intrinsic programs or are influenced their environmental contexts. Multiple transcription regulators chromatin modifiers contribute alterations. Special AT‐rich sequence‐binding protein 1 (SATB1) stands out crucial regulator this process, orchestrating expression structuring into loop domains anchoring DNA elements. This review provides overview senescence delves role SATB1 senescence‐related diseases. highlights SATB1's potential developing antiaging anticancer strategies, potentially contributing improved quality life addressing aging‐related

Language: Английский

Citations

2
A new model of human lymphopoiesis across development and aging DOI
Kutaiba Alhaj Hussen,

Valentine Louis,

Bruno Canque

et al.

Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(7), P. 495 - 510

Published: June 21, 2024

Language: Английский

Citations

2