Since the 1990s, journals have become increasingly online and open access. In fact, about 50% of articles published in 2021 were open access. The use of preprints (i.e., non‐peer‐reviewed articles) ...has also increased. However, there is limited awareness of these concepts among academics. Therefore, we conducted a questionnaire‐based survey among members of the Molecular Biology Society of Japan. The survey was conducted between September 2022 and October 2022, with 633 respondents, 500 of whom (79.0%) were faculty members. In total, 478 (76.6%) respondents had published articles as open access, and 571 (91.5%) wanted to publish their articles in open access. Although 540 (86.5%) respondents knew about preprints, only 183 (33.9%) had posted preprints before. In the open‐ended section of the questionnaire survey, several comments were made about the cost burdens associated with open access and the difficulty of how academic preprints are handled. Although open access is widespread, and recognition of preprints is increasing, some issues remain that need to be addressed. Academic and institutional support, and transformative agreement may help reduce the cost burden. Guidelines for handling preprints in academia are also important for responding to changes in the research environment.
Heterochromatin plays important roles in transcriptional silencing and genome maintenance by the formation of condensed chromatin structures, which determine the epigenetic status of eukaryotic ...cells. The trimethylation of histone H3 lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of heterochromatin formation. However, the mechanism by which HP1 folds chromatin-containing H3K9me3 into a higher-order structure has not been elucidated. Here we report the three-dimensional structure of the H3K9me3-containing dinucleosomes complexed with human HP1α, HP1β, and HP1γ, determined by cryogenic electron microscopy with a Volta phase plate. In the structures, two H3K9me3 nucleosomes are bridged by a symmetric HP1 dimer. Surprisingly, the linker DNA between the nucleosomes does not directly interact with HP1, thus allowing nucleosome remodeling by the ATP-utilizing chromatin assembly and remodeling factor (ACF). The structure depicts the fundamental architecture of heterochromatin.
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•The HP1-H3K9me3 dinucleosome complex structure determined by the cryo-EM method•HP1 forms a symmetric dimer and bridges two H3K9me3 nucleosomes in the complex•The HP1 chromoshadow domain dimer exists in an accessible location in the complex•The linker DNA between nucleosomes does not directly interact with HP1
HP1 and H3 Lys9 trimethylations (H3K9me3) are hallmarks of heterochromatin, and they play pivotal roles in the epigenetic propagation of heterochromatin. Machida et al. describe the structure of the H3K9me3-containing dinucleosome complexed with human HP1, obtained by the cryo-EM technique.
Heterochromatin protein 1 (HP1) is an evolutionarily conserved chromosomal protein that binds lysine 9-methylated histone H3 (H3K9me), a hallmark of heterochromatin, and plays a crucial role in ...forming higher-order chromatin structures. HP1 has an N-terminal chromodomain and a C-terminal chromo shadow domain, linked by an unstructured hinge region. Although biochemical and structural studies have revealed each domain's properties, little is known about the mechanisms by which these domains cooperate to carry out HP1's function in forming higher-order chromatin structures. In this review, we summarize HP1's biochemical and structural properties and highlight the latest findings regarding HP1's interactions with nucleosomes.
The methylation of histone H3 at lysine 9 (H3K9me), performed by the methyltransferase Clr4/SUV39H, is a key event in heterochromatin assembly. In fission yeast, Clr4, together with the ubiquitin E3 ...ligase Cul4, forms the Clr4 methyltransferase complex (CLRC), whose physiological targets and biological role are currently unclear. Here, we show that CLRC‐dependent H3 ubiquitylation regulates Clr4's methyltransferase activity. Affinity‐purified CLRC ubiquitylates histone H3, and mass spectrometric and mutation analyses reveal that H3 lysine 14 (H3K14) is the preferred target of the complex. Chromatin immunoprecipitation analysis shows that H3K14 ubiquitylation (H3K14ub) is closely associated with H3K9me‐enriched chromatin. Notably, the CLRC‐mediated H3 ubiquitylation promotes H3K9me by Clr4, suggesting that H3 ubiquitylation is intimately linked to the establishment and/or maintenance of H3K9me. These findings demonstrate a cross‐talk mechanism between histone ubiquitylation and methylation that is involved in heterochromatin assembly.
Synopsis
The Clr4 methyltransferase complex in fission yeast preferentially ubiquitylates H3K14. H3K14ub is linked to H3K9me‐enriched heterochromatin and promotes Clr4 methyltransferase activity.
The Clr4 methyltransferase complex (CLRC) preferentially ubiquitylates H3K14.
K14‐ubiquitylated histone H3 is enriched in heterochromatin.
CLRC‐mediated H3 ubiquitylation promotes Clr4 methyltransferase activity.
The Clr4 methyltransferase complex in fission yeast preferentially ubiquitylates H3K14. H3K14ub is linked to H3K9me‐enriched heterochromatin and promotes Clr4 methyltransferase activity.
Abstract
In eukaryotic cells, DNA is tightly compacted as chromatin. Chromatin states must be dynamically changed to increase the accessibility of transcription factors (TFs) to chromatin or to ...stably silence genes by higher-order chromatin structures known as heterochromatin. The regulation of chromatin needs cooperative action performed by a variety of proteins. Specific binding of TFs to target DNA is the initial step of chromatin regulation and promotes changes in the post-translational modifications of histone tails, which themselves are recognized by a set of histone reader proteins. Recent biochemical studies have revealed that some TFs that recognize specific DNA sequences can also interact with histones. Furthermore, histone reader proteins that recognize specific histone tail modifications have been shown to have the ability to directly bind to DNA. In this commentary, we introduce recent advances in the elucidation of how chromatin regulating factors recognize nucleosomal targets.
Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are ...evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases.
SUV39H is the major histone H3 lysine 9 (H3K9)-specific methyltransferase that targets pericentric regions and is crucial for assembling silent heterochromatin. SUV39H recognizes trimethylated H3K9 ...(H3K9me3) via its chromodomain (CD), and enriched H3K9me3 allows SUV39H to target specific chromosomal regions. However, the detailed targeting mechanisms, especially for naïve chromatin without preexisting H3K9me3, are poorly understood. Here we show that Suv39h1's CD (Suv39h1-CD) binds nucleic acids, and this binding is important for its function in heterochromatin assembly. Suv39h1-CD had higher binding affinity for RNA than DNA, and its ability to bind nucleic acids was independent of its H3K9me3 recognition. Suv39h1 bound major satellite RNAs
, and knockdown of major satellite RNAs lowered Suv39h1 retention on pericentromere. Suv39h1 mutational studies indicated that both the nucleic acid-binding and H3K9me-binding activities of Suv39h1-CD were crucial for its pericentric heterochromatin assembly. These results suggest that chromatin-bound RNAs contribute to creating SUV39H's target specificity.
Biliary tract cancer (BTC) is typically lethal due to the difficulty of early stage diagnosis. Thus, novel biomarkers of BTC precursors are necessary. Biliary intraepithelial neoplasia (BilIN) is a ...major precursor of BTC and is classified as low or high grade based on cell atypia. In normal gastric mucosa, gastric gland mucin‐specific O‐glycans are unique in having α1,4‐linked N‐acetylglucosamine (αGlcNAc) attached to MUC6. Previously, we reported that αGlcNAc functions as a tumor suppressor of differentiated‐type gastric adenocarcinoma and that decreased αGlcNAc glycosylation on MUC6 in gastric, pancreatic, and uterine cervical neoplasms occurs in cancer as well as in their precursor lesions. However, αGlcNAc and MUC6 expression patterns in biliary tract neoplasms have remained unclear. Here, we analyzed MUC5AC, MUC6, and αGlcNAc expression status in 51 BTC cases and compared the expression of each with progression from low‐grade BilIN to invasive adenocarcinoma (IAC). The frequency of αGlcNAc‐positive and MUC6‐positive lesions decreased with tumor progression. When we compared each marker’s expression level with tumor progression, we found that the MUC6 expression score in IAC was significantly lower than in low‐grade or high‐grade BilIN (P < 0.001 or P < 0.01, respectively). However, the αGlcNAc expression score was low irrespective of histological grade, and also lower than that of MUC6 across all histological grades (P < 0.001 for low‐grade and high‐grade BilIN, and P < 0.01 for IAC). These results suggest that decreased expression of αGlcNAc relative to MUC6 marks the initiation of BTC progression.
Alpha‐1,4‐linked N‐acetylglucosamine glycosylation on MUC6 is already decreased in biliary intraepithelial neoplasia.
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