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The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.
Sci Rep
December 2024
Department of Psychiatry and Behavioral Sciences and Weill Center for Neurosciences, University of California, San Francisco, CA, 94107, USA.
Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.
View Article and Find Full Text PDFThe proximity ligation-based Hi-C and derivative methods are the mainstream tools to study genome-wide chromatin interactions. These methods often fragment the genome using enzymes functionally irrelevant to the interactions per se, restraining the efficiency in identifying structural features and the underlying regulatory elements. Here we present Footprint-C, which yields high-resolution chromatin contact maps built upon intact and genuine footprints protected by transcription factor (TF) binding.
View Article and Find Full Text PDFDDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.
Nat Commun
December 2024
Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia University Irving Medical Center, New York, NY, USA.
Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.
View Article and Find Full Text PDFStructural insights into how Cas9 targets nucleosomes.
Nat Commun
December 2024
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
The CRISPR-associated endonuclease Cas9 derived from prokaryotes is used as a genome editing, which targets specific genomic loci by single guide RNAs (sgRNAs). The eukaryotes, the target of genome editing, store their genome DNA in chromatin, in which the nucleosome is a basic unit. Despite previous structural analyses focusing on Cas9 cleaving free DNA, structural insights into Cas9 targeting of DNA within nucleosomes are limited, leading to uncertainties in understanding how Cas9 operates in the eukaryotic genome.
View Article and Find Full Text PDFMulticopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes.
Nat Commun
December 2024
State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C.
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