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In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties were originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate . We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays.
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http://dx.doi.org/10.1101/2023.09.18.558303 | DOI Listing |
Blood Adv
September 2025
Institut de Recherches Cliniques de Montreal - IRCM, Montreal, Quebec, Canada.
Acute myeloid leukemia (AML) with rearrangement of the mixed lineage leukemia gene express MLL-AF9 fusion protein, a transcription factor that impairs differentiation and drives expansion of leukemic cells. We report here that the zinc finger protein GFI1 together with the histone methyltransferase LSD1 occupies the promoter and regulates expression of the lncRNA ELDR in the MLL-r AML cell line THP-1. Forced ELDR overexpression enhanced the growth inhibition of an LSD1i/ATRA combination treatment and reduced the capacity of these cells to generate leukemia in xenografts, leading to a longer leukemia-free survival.
View Article and Find Full Text PDFCell Rep Methods
July 2025
Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China; Key Laboratory of Smart Farming for Agricultural Animals, Ministry of Agriculture and Rural Affairs, Beijing, P.R. China; College of Informatics, Huazhong Agricult
We introduce a cell-free DNA (cfDNA) fragmentation pattern: the fragment dispersity index (FDI), which integrates information on the distribution of cfDNA fragment ends with the variation in fragment coverage, enabling precise characterization of chromatin accessibility in specific regions. The FDI shows a strong correlation with chromatin accessibility and gene expression, and regions with high FDI are enriched in active regulatory elements. Using whole-genome cfDNA data from five datasets, we developed and validated the FDI-oncology model, which demonstrates robust performance in early cancer diagnosis, subtyping, and prognosis.
View Article and Find Full Text PDFMultiple myeloma (MM) continues to be an incurable malignancy, even with recent therapeutic advancements. While epigenetic dysregulation at cis-regulatory elements is known to drive disease progression, the complete molecular mechanisms underlying these alterations are poorly understood. Using ATAC-seq analysis combined with computational footprinting of CD138+ cells from 55 MM patients, we depicted the dynamic changes in chromatin accessibility during disease progression and identified Nuclear Respiratory Factor 1 (NRF1) as a master regulator of vital MM survival pathways.
View Article and Find Full Text PDFElife
September 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Innate immune cells can acquire a memory phenotype, termed trained immunity, but the mechanism underlying the regulation of trained immunity remains largely elusive. Here, we demonstrate that inhibition of Aurora kinase A (AurA) dampens trained immunity induced by β-glucan. ATAC-seq and RNA-seq analysis reveal that AurA inhibition restricts chromatin accessibility of genes associated with inflammatory pathways such as JAK-STAT, TNF, and NF-κB pathways.
View Article and Find Full Text PDFNAR Cancer
September 2025
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
Noncoding RNAs play pivotal roles in tumorigenesis and cancer progression. Recent evidence has identified vault RNAs (vtRNAs) as critical regulators of cellular homeostasis. The human genome encodes four vtRNA paralogs, which are differentially expressed in cancer tissues and contribute to tumor development.
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