BRD7 inhibits enhancer activity and expression of BIRC2 to suppress tumor growth and metastasis in nasopharyngeal carcinoma DOI Creative Commons
Mengna Li,

Yanmei Wei,

Yukun Liu

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 14, 2023

Abstract BRD7 functions as a crucial tumor suppressor in numerous malignancies including nasopharyngeal carcinoma (NPC). However, its function and exact mechanisms involved progression are not well understood. Here, we found that the B7BS was potential enhancer region of BIRC2, negatively regulated transcriptional activity expression BIRC2 by targeting activation enhancer. Moreover, promoted cell proliferation, migration, invasion xenograft growth metastasis vivo, thus functioning an oncogene NPC. Furthermore, recovery could rescue inhibitory effect on metastasis. In addition, highly-expressed NPC tissues, positively correlated with TNM stage BRD7. Therefore, these results suggest suppresses at least partially regulating BRD7/BIRC2 regulation axis might be strategy for diagnosis treatment

Language: Английский

Structural insights into nuclear transcription by eukaryotic DNA-dependent RNA polymerases DOI
Mathias Girbig, Agata D. Misiaszek, Christoph W. Müller

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(9), P. 603 - 622

Published: May 3, 2022

Language: Английский

Citations

81
3D enhancer-promoter interactions and multi-connected hubs: Organizational principles and functional roles DOI Creative Commons

Christopher M Uyehara,

Effie Apostolou

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112068 - 112068

Published: April 1, 2023

The spatiotemporal control of gene expression is dependent on the activity cis-acting regulatory sequences, called enhancers, which regulate target genes over variable genomic distances and, often, by skipping intermediate promoters, suggesting mechanisms that enhancer-promoter communication. Recent genomics and imaging technologies have revealed highly complex interaction networks, whereas advanced functional studies started interrogating forces behind physical communication among multiple enhancers promoters. In this review, we first summarize our current understanding factors involved in communication, with a particular focus recent papers new layers complexities to old questions. second part subset connected "hubs" discuss their potential functions signal integration regulation, as well putative might determine dynamics assembly.

Language: Английский

Citations

81
Donafenib and GSK‐J4 Synergistically Induce Ferroptosis in Liver Cancer by Upregulating HMOX1 Expression DOI Creative Commons

Chenyang Zheng,

Bo Zhang, Yunyun Li

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: June 17, 2023

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Donafenib a multi‐receptor tyrosine kinase inhibitor approved for treatment patients with advanced HCC, but its clinical effect very limited. Here, through integrated screening small‐molecule library and druggable CRISPR library, that GSK‐J4 synthetically donafenib in liver cancer shown. This synergistic lethality validated multiple HCC models, including xenograft, orthotopically induced patient‐derived organoid models. Furthermore, co‐treatment resulted cell death mainly via ferroptosis. Mechanistically, RNA sequencing (RNA‐seq) assay transposase‐accessible chromatin high throughput (ATAC‐seq) analyses, synergistically promoted expression HMOX1 increased intracellular Fe2+ level found, eventually leading to Additionally, cleavage under targets & tagmentation followed by (CUT&Tag‐seq), it found enhancer regions upstream promoter significantly co‐treatment. A chromosome conformation capture confirmed caused enhanced interaction between dual‐drug combination. Taken together, this study elucidates new cancer.

Language: Английский

Citations

67
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation DOI
Jin Yang, Anders S. Hansen

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 574 - 591

Published: Feb. 27, 2024

Language: Английский

Citations

51
Transcription factor clusters as information transfer agents DOI Creative Commons
Rahul Munshi, Ling Jia, Sergey Ryabichko

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging fluorescently tagged Bicoid living Drosophila embryos, we show that accumulation submicrometer clusters preserves spatial maternal gradient. These provide precise cues through intensity, size, and frequency. We further discover target colocalize with these an enhancer-binding affinity-dependent manner. Our modeling suggests clustering offers faster sensing mechanism for global nuclear than freely diffusing molecules detected by simple enhancers.

Language: Английский

Citations

4
SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape DOI Creative Commons
Shibin Hu, Linna Peng, Congling Xu

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(21), P. 4425 - 4439.e6

Published: Sept. 16, 2021

Transcription progression is governed by multitasking regulators including SPT5, an evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer activation to termination. Here we utilize a rapid degradation system and reveal crucial functions of SPT5 maintaining cellular chromatin RNA polymerase II (Pol II) levels. Rapid depletion causes pronounced reduction paused Pol at promoters enhancers, distinct negative elongation (NELF) resulting short-distance redistribution. Most genes exhibit downregulation, but not upregulation, accompanied greatly impaired transcription activation, altered landscape severe processivity defects gene bodies. Phosphorylation linker serine 666 potentiates pause release antagonized Integrator-PP2A (INTAC) targeting II, while phosphorylation the C-terminal region links 3′ end Our findings position as essential positive regulator global transcription.

Language: Английский

Citations

83
Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation DOI
Wentao Han,

Liangjie Liu,

Jing Wang

et al.

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(12), P. 1891 - 1906

Published: Oct. 24, 2022

Language: Английский

Citations

47
Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes DOI Creative Commons
Ferdinand Marlétaz, Arnaud Couloux, Julie Poulain

et al.

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(4), P. 100295 - 100295

Published: April 1, 2023

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues may underlie these specificities, we generated a chromosome-scale genome assembly for sea urchin Paracentrotus lividus an extensive gene expression epigenetic profiles of its embryonic development. We found that, unlike vertebrates, retained ancestral chromosomal linkages but underwent very fast intrachromosomal order mixing. identified burst duplication echinoid lineage showed some expanded genes have been recruited novel structures (water vascular system, Aristotle's lantern, skeletogenic micromere lineage). Finally, gene-regulatory modules conserved between chordates. Our results suggest networks controlling development can be despite rearrangement.

Language: Английский

Citations

34
Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions DOI Creative Commons
Lizhen Chen, Zhao Zhang, Qinyu Han

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(19), P. 3438 - 3456.e12

Published: Sept. 21, 2023

Language: Английский

Citations

26
Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases DOI Creative Commons
Priyanka Dey Talukdar, Urmi Chatterji

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 13, 2023

Abstract Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and co-activators. Deregulation these regulatory molecules is associated with state transitions, which turn accountable for diverse maladies, including developmental disorders, metabolic most significantly, cancer. A decade back factors, key enablers disease development, were historically viewed as ‘undruggable’; however, intervening years, a wealth literature validated they can be targeted indirectly through transcriptional co-activators, their confederates various physiological molecular processes. These along have ability to initiate modulate genes necessary normal functions, whereby, deregulation such may foster tissue-specific phenotype. Hence, it essential analyze how co-activators specific multilateral processes coordination other factors. The proposed review attempts elaborate an in-depth account involvement regulation, context-specific contributions pathophysiological conditions. This also addresses issue has not been dealt comprehensive manner hopes direct attention towards future research will encompass patient-friendly therapeutic strategies, where drugs targeting enhanced benefits reduced side effects. Additional insights into currently available interventions constraints eventually reveal multitudes advanced targets aiming amelioration good patient prognosis.

Language: Английский

Citations

26