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The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organisation and dynamics of chromatin compacted by gene-repressing factors are unknown. Using cryo-electron tomography, we solved the three-dimensional structure of chromatin condensed by the Polycomb Repressive Complex 1 (PRC1) in a complex with CBX8. PRC1-condensed chromatin is porous and stabilised through multivalent dynamic interactions of PRC1 with chromatin. Mechanistically, positively charged residues on the internally disordered regions (IDRs) of CBX8 mask negative charges on the DNA to stabilize the condensed state of chromatin. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure. In differentiated mouse embryonic stem cells, CBX8-bound chromatin remains accessible. These findings challenge the idea of rigidly compacted polycomb domains and instead provides a mechanistic framework for dynamic and accessible PRC1-chromatin condensates.
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http://dx.doi.org/10.1101/2023.05.08.539931 | DOI Listing |
OMICS
September 2025
Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore, India.
Wings apart-like protein (WAPL) has emerged as a key player in maintaining genome integrity through its regulation of cohesin dynamics, which govern chromatin architecture and gene expression. WAPL mainly acts as a cohesin release factor and ensures proper chromosomal segregation during mitosis by promoting sister chromatid resolution. Owing to its prominent role in cell biology, WAPL dysregulation can cause genomic instability and disrupt chromosomal cohesion, leading to diseases such as cancer.
View Article and Find Full Text PDFBMB Rep
September 2025
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
DNA, a large molecule located in the nucleus, carries essential genetic information, including gene loci and cis-regulatory elements. Despite its extensive length, DNA is compactly stored within the limited space of the nucleus due to its hierarchical three-dimensional (3D) organization. In this structure, DNA is organized into territories known as topologically associated domains (TADs).
View Article and Find Full Text PDFJ Genet Genomics
September 2025
Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Sh
Chromodomain helicase DNA binding protein 7 (CHD7), an ATP-dependent chromatin remodeler, plays versatile roles in neurodevelopment. However, the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood. Here, we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.
View Article and Find Full Text PDFBehav Brain Res
September 2025
Department of neurology, Hebei Medical University Third Hospital, Hebei 050000,Shijiazhuang,China; Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Hebei 050000,Shijiazhuang,China. Electronic address:
Background: Mitochondrial dysfunction is considered to be an important pathogenesis of cognitive impairment in Alzheimer's disease(AD). Activation of Nrf2 can improve cognitive impairment in AD mice, but the underlying mechanism remains to be elucidated. This research aims to investigate the intrinsic molecular mechanism of Nrf2 in mitochondrial biogenesis related to cognitive impairment of AD mice.
View Article and Find Full Text PDFJ Ethnopharmacol
September 2025
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou Province, China. Electronic address:
Ethnopharmacological Relevance: Gastrodia elata, also known as Chijian, belongs to the Orchidaceae family of plants. The "Compendium of Materia Medica" records that Gastrodia elata treats "confused speech, excessive fear, and loss of willpower". Gastrodin (GAS) is the main bioactive component of Gastrodia elata.
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