Genes to Cells最新文献

Calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ), encoded by the Camk2d gene, plays key regulatory roles in various Ca²⁺-regulated cellular processes. Extensive alternative splicing of the Camk2d gene generates multiple CaMKIIδ splice variants that exhibit differential roles. Despite significant advances in understanding the functions of CaMKIIδ, the full repertoire of Camk2d splice variants in a variety of tissues and their distinct roles in physiological and pathological contexts remain incompletely characterized due to the complex nature of multiple alternative splicing events. Here, we conducted long-read amplicon sequencing to investigate the murine Camk2d splice variants in the heart, skeletal muscle, and olfactory bulbs and show that mRNAs in the heart and skeletal muscle have shorter 3'UTRs. Our results in this study suggest that a key regulator of Camk2d splicing, RNA-binding motif protein 20 (RBM20), whose gain-of-function mutations cause dilated cardiomyopathy, is crucial for the expression of heart-specific splice variants. Olfactory bulbs specifically express novel splice variants that utilize a mutually exclusive exon 6B and/or an alternative polyadenylation site in a novel exon 17.5 in an RBM20-independent manner. The tissue-specific repertoire of CaMKIIδ splice variants and their aberrant expression in disease model animals will help in understanding their roles in physiological and pathological contexts.

Chromatin restructuring across multiple hierarchical scales directs lineage-specific gene expression during cell differentiation. Here, we investigated the iron-dependent demethylation of histone H3 lysine 9 dimethylation (H3K9me2) by the demethylase jumonji domain-containing 1A (JMJD1A) in adipocyte differentiation. Using the 3T3-L1 adipocyte differentiation model, we show that JMJD1A knockdown increases H3K9me2 levels, whereas forced expression of wild-type JMJD1A reduces H3K9me2 levels within the A compartment, as defined by megabase scale high-throughput chromosome conformation capture (Hi-C) data. In contrast, a JMJD1A mutant defective in iron coordination was unable to demethylate H3K9me2. Genome-wide analyses of H3K9me2 levels at transcription start sites on a kilobase scale demonstrated that JMJD1A targets genes involved in peroxisome proliferator-activated receptor signaling and lipid metabolism in an iron-dependent manner, supporting a model in which H3K9me2 demethylation facilitates adipogenic transcription networks. Furthermore, we examined the relationship between H3K9me2 and lamin B1 levels within lamina-associated domains (LADs) specifically reorganized during differentiation. Although LADs with higher H3K9me2 exhibited modestly elevated lamin B1 association in preadipocytes, lamin B1 levels declined during differentiation regardless of H3K9me2 status. These findings emphasize the importance of the iron-dependent enzymatic function in JMJD1A and broaden our understanding of how specific H3K9 demethylases coordinate compartmentalized epigenetic programs during adipogenesis.

Kohyanagi, N., and T. Ohama. 2023. “The Impact of SETBP1 Mutations in Neurological Diseases and Cancer.” Genes to Cells 28, no. 9: 629–641. https://doi.org/10.1111/gtc.13057.

We would like to sincerely thank the reader's comments regarding Table 1. After reviewing the suggestions, we have identified and acknowledged several inaccuracies in the original table listing SETBP1 variants.

We mistakenly described frameshift variants cited by Coe et al. (2014) as missense variants. We also incorrectly labeled the associated disease as Schinzel–Giedion syndrome (SGS) instead of intellectual disability (ID), which would have been appropriate.

We apologize for the oversight and any confusion or misinterpretation this may have caused.

In eukaryotic cells, genomic DNA is compacted by nucleosomes, as basic repeating units, into chromatin. The nucleosome arrangement in chromatin fibers could be an important determinant for chromatin folding, by which genomic DNA is regulated in the nucleus. To study the structures of chromatin units in cells, we have established a method for the structural analysis of native mono- and poly-nucleosomes prepared from HeLa cells. In this method, the chromatin in isolated nuclei was crosslinked to preserve the proximity information between nucleosomes, followed by chromatin fragmentation by micrococcal nuclease treatment. The mono- and poly-nucleosomes were then fractionated by sucrose gradient ultracentrifugation, and their structures were analyzed by cryo-electron microscopy. Cryo-electron microscopy single particle analysis and cryo-electron tomography visualized a native nucleosome structure and secondary nucleosome arrangements in cellular chromatin. This method provides a complementary strategy to fill the gap between in vitro and in situ analyses of chromatin structure.

In eukaryotes, genomic DNA is stored in the nucleus as nucleosomes, in which a DNA segment is wrapped around a protein octamer consisting of two each of the four histones, H2A, H2B, H3, and H4. The core histones can be replaced by histone variants or altered with covalent modifications, contributing to the regulation of chromosome structure and nuclear activities. The formation of an octameric histone core in nucleosomes is widely accepted. Recently, the H3–H4 octasome, a novel nucleosome-like structure with a histone octamer consisting solely of H3 and H4, has been reported. CENP-A is the centromere-specific histone H3 variant and determines the position of kinetochore assembly during mitosis. CENP-A is a distant H3 variant sharing approximately 50% amino acid sequence with H3. In this study, we found that CENP-A and H4 also formed an octamer without H2A and H2B in vitro. We determined the structure of the CENP-A–H4 octasome at 3.66 Å resolution. In the CENP-A–H4 octasome, an approximately 120-base pair DNA segment was wrapped around the CENP-A–H4 octameric core and displayed the four CENP-A RG-loops, which are the direct binding sites for another centromeric protein, CENP-N.

Chen, P., and M. Umeda. 2015. “DNA double-strand breaks induce the expression of flavin-containing monooxygenase and reduce root meristem size in Arabidopsis thaliana.” Genes to Cells 20, no. 8: 636–646. https://doi.org/10.1111/gtc.12255.

We apologize for this error.