Histones are the major protein component of nucleosomes, and de novo histone synthesis is essential for packaging newly replicated DNA into chromatin. As a result, histone gene expression is exquisitely and functionally coupled with DNA replication. Vastly divergent organisms such as yeast, fly and human all demonstrate the phylogenetically conserved propensity to maintain clustering of histone genes at one or more genomic loci. Although specific mechanisms are unclear, clustering is presumed to be important for common stringent transcriptional control of these genes at the G1/S phase transition. In this study, we describe a genomic duplication of the human histone gene cluster located at chromosome 1q21, which effectively doubles the previously known size and gene number of that cluster. The duplication persists in all examined tissues and cell lines, and the duplicated genes are transcriptionally active. Levels of messenger RNAs for duplicated histone H4 genes are high relative to those for non-duplicated H4 genes. Our data suggest that transcriptionally robust histone H4 genes may have been preferentially duplicated during evolution.
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http://dx.doi.org/10.1016/j.gene.2004.07.036 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.
View Article and Find Full Text PDFChem Biol Drug Des
January 2025
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Hepatocellular carcinoma (HCC) presents an escalating public health challenge globally. However, drug resistance has emerged as a major impediment to successful HCC treatment, limiting the efficacy of curative interventions. Despite numerous investigations into the diverse impacts of hsa-miR-125a-5p on tumor growth across different cancer types, its specific involvement in chemotherapy resistance in HCC remains elusive.
View Article and Find Full Text PDFFASEB J
January 2025
Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Lung cancer progression is characterized by intricate epigenetic changes that impact critical metabolic processes and cell death pathways. In this study, we investigate the role of histone lactylation at the AIM2 locus and its downstream effects on ferroptosis regulation and lung cancer progression. We utilized a combination of biochemical assays, including chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and western blotting to assess histone lactylation levels and gene expression.
View Article and Find Full Text PDFExpert Rev Anticancer Ther
January 2025
Department of Physiology, Pomeranian Medical University in Szczecin, Poland.
Introduction: Histone modifications are crucial epigenetic mechanisms for regulating gene expression. Histone acetyltransferases and deacetylases (HDACs) catalyze histone acetylation, a process that mediates transcription. Over recent decades, studies have demonstrated that targeting histone acetylation can be effective in cancer treatment, leading to the development and approval of several HDAC inhibitors.
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