Patterns of histone binding to DNA of transcriptionally active D. melanogaster hsp70 genes within the nuclei have been analyzed by two methods of histone-DNA chemical cross-linking. When cross-linking is restricted to the central, "globular" regions of histones, it drops most for H1, to an intermediate extent for H2A and H2B, and least for H3 and H4 in transcriptionally active versus transcriptionally silent chromatin. When it occurs via histone terminal regions as well, cross-linking is quantitatively similar for active and inactive chromatin. Neither cross-linking method detects histones on the hsp70 promoter region. It appears that chromatin activation decreases histone binding to DNA via the "globular" regions, known to be essential for the folding of nucleosomes and the 30 nm chromatin fibril, but does not significantly affect the interaction of flexible and loosely bound histone "tails" with DNA. The role of these histone-DNA interaction changes in the unfolding of active chromatin and RNA polymerase reading through histone-bound DNA is discussed.
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Acta Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.
View Article and Find Full Text PDFEMBO Rep
January 2025
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Transcriptional regulation governs gene expression levels, primarily controlled by "cis-acting DNA elements" and "trans-acting protein factors". However, the conventional view that cis-regulation is solely attributable to DNA elements is challenged in this study. Our research indicates that transposon-derived proteins may retain their original DNA-binding preference and exert cis-regulatory effects on nearby genes on the chromosome, thus denoted as "cis-acting factors".
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
University of California, Berkeley─University of California, San Francisco Graduate Program in Bioengineering, San Francisco, California 94158, United States.
Neutrophil extracellular traps (NETs) are networks of decondensed chromatin, histones, and antimicrobial proteins released by neutrophils in response to an infection. NET overproduction can cause an exacerbated hyperinflammatory response in a variety of diseases and can lead to host tissue damage without clearance of infection. Nanoparticle drug delivery is a promising avenue for creating materials that can both target NETs and deliver sustained amounts of NET-degrading drugs to alleviate hyperinflammation.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia. Electronic address:
Background: Melanoma, a highly aggressive skin cancer is frequently driven by the BRAF mutation. Vemurafenib initially offers clinical benefits but often encounters resistance due to secondary mutations and compensatory signaling pathways. Targeting p300, a histone acetyltransferase involved in transcriptional regulation and resistance mechanisms, presents a potential strategy to overcome this therapeutic challenge.
View Article and Find Full Text PDFCell Mol Biol Lett
January 2025
Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Key Laboratory of Drug Research for Prevention and Treatment of Hyperlipidemic Diseases, Soochow University, 199 Ren'ai Road, Suzhou, 215123, Jiangsu, China.
Background: The protein cereblon (CRBN) mediates the antileukemia effect of lenalidomide (Len). Len binds to CRBN, recruits IKZF1/IKZF3, and promotes their ubiquitination and degradation, through which Len exhibits its antileukemia and antimyeloma activity. Therefore, the protein level of CRBN might affect the antiproliferative effect of Len.
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