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The chromatin structure of several Saccharomyces cerevisiae ADR1-dependent genes was comparatively analyzed in vivo in order to evaluate the role of promoter architecture in transcriptional control. In repressing conditions (high glucose) a nucleosome particle always obstructs the TATA box, immediately adjacent to an upstream-located nucleosome-free region containing a cluster of Adr1 binding sites. Upon derepression the TATA box-containing nucleosome is destabilized according to a mechanism shared by all of the genes studied. The transcription factor Adr1 is always required for the observed chromatin remodeling. mRNA accumulation of all of the genes analyzed is strongly delayed in the absence of the acetyltransferase Gcn5 and is decreased in the presence of a temperature-sensitive Esa1 mutant. The results suggest that a defined promoter chromatin structure, controlled by DNA conformational features, is relevant for the activation of coregulated genes.
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http://dx.doi.org/10.1021/bi049577+ | DOI Listing |
Front Immunol
September 2025
Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Gliomas are the most common primary malignant tumors of the central nervous system (CNS), and despite progress in molecular diagnostics and targeted therapies, their prognosis remains poor. In recent years, immunotherapy has emerged as a promising treatment modality in cancer therapy. However, the inevitable immune evasion by tumor cells is a key barrier affecting therapeutic efficacy.
View Article and Find Full Text PDFProtoplasma
September 2025
Vavilov Institute of General Genetics RAS, Moscow, Russia.
Large interstitial telomeric regions are considered remnants and markers of chromosomal rearrangements or a result of several suggested molecular mechanisms of telomere repeats accumulation. More rare are cases when large interstitial repeats are found not close to, but at a distance from the centromere. However, synapsis, recombination, and effects on chromatin near these regions during meiotic prophase I have not been sufficiently studied.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam 3000 CA, the Netherlands.
Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this domain result in a distinctive cortical and brain stem malformation.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
Department of Infectious Diseases, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
Histones were once thought to be exclusive to the nucleus, but were recently discovered in the extracellular space, where they play important roles in disease pathogenesis. In addition to their traditional functions in chromatin organization and gene regulation, extracellular histones also serve as damage-associated molecular patterns (DAMPs), drive inflammation and immune responses, and are responsible for the progression of diseases such as sepsis, autoimmune diseases, and inflammatory diseases. To effectively target extracellular histones and improve disease progression, this review begins with the release and pathogenic mechanisms of histones and explains the main pathogenic mechanisms of extracellular histones in many diseases.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Background: Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.
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