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As superfamily 2 (SF2)-type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers.
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http://dx.doi.org/10.7554/eLife.34100 | DOI Listing |
Mitochondrial DNA A DNA Mapp Seq Anal
September 2025
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
Hibernation is an elaborate response strategy employed by numerous mammals to survive in cold conditions that involves active suppression of metabolism. Despite the role of mitochondria as energy metabolism centers during hibernation, the adaptive and evolutionary mechanisms of mitochondrial genes in hibernating animals, like hedgehogs in eulipotyphlan species, are not yet fully understood. In this study, we sequenced and assembled mitochondrial genomes of the hibernating four-toed hedgehog () and the non-hibernating Asian house shrew ().
View Article and Find Full Text PDFHistol Histopathol
September 2025
Center for Experimental Teaching, School of Pharmacy, Guangzhou Medical University, Guangzhou, China.
Background: The aim of this study was to establish a rat model of premature ovarian failure (POF) with cyclophosphamide (CTX), and explore the molecular basis of POF and the mechanism of Guishen-Erxian Decoction (GSEXD) to improve POF from the perspective of oxidative stress regulation of ovarian granulosa cell (OGC) DNA fragmentation.
Method: The study utilized SD rats to establish a POF model via CTX. Rats were divided into Control, POF group, three GSEXD dosage groups (low, medium, high), and a GSEXD+PI3K agonist group to assess GSEXD's therapeutic effects on oxidative stress, DNA fragmentation and ovarian damage.
Mol Cancer Ther
September 2025
Case Western Reserve University School of Medicine, Cleveland, OH, United States.
The estrogen receptor (ER or ERα) remains the primary therapeutic target for luminal breast cancer, with current treatments centered on competitive antagonists, receptor down-regulators, and aromatase inhibitors. Despite these options, resistance frequently emerges, highlighting the need for alternative targeting strategies. We discovered a novel mechanism of ER inhibition that targets the previously unexplored interface between the DNA-binding domain (DBD) and ligand-binding domain (LBD) of the receptor.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
September 2025
Faculty of Medicine, Department of Physiology, University of Iceland, Reykjavik (G.K.).
Biological sex influences the life course development of blood pressure, systemic arterial hypertension, and hypertension-associated complications through neural, hormonal, renal, and epigenetic mechanisms. Sex hormones influence blood pressure regulation through interaction with several main regulatory systems, including the autonomic nervous system, the renin-angiotensin-aldosterone system, endothelin, and renal mechanisms. The modulation of vascular function by sex hormones varies over the lifespan.
View Article and Find Full Text PDFHypertension
September 2025
Department of Obstetrics and Gynecology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu (Z.W.).
Background: Early-onset preeclampsia poses significant risks to maternal and fetal health, necessitating a deeper understanding of its molecular mechanisms and effective therapeutic strategies.
Methods: Utilizing data from genome-wide association study and Mendelian randomization analysis, we investigated the relationship between mitochondrial DNA copy number and preeclampsia. Transcriptome sequencing, in vitro experiments, and animal studies were conducted to explore the roles of SENP3 and SETD7 in preeclampsia pathogenesis.