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Publisher's expression of concern.

The American Society for Microbiology (ASM) and Molecular and Cellular Biology (MCB) are issuing this Expression of Concern to alert readers to doubts about the integrity of the data in papers coauthored by Dr. Shigeaki Kato. In 2012, ASM was notified that the University of Tokyo Institute of Molecular and Cellular Biosciences is conducting an investigation of possible scientific misconduct by Dr. Kato. Among the publications under investigation for possible data manipulation are these five MCB articles. The Expression of Concern is only for papers coauthored by Dr. Kato that have been publish

SKY assessment of two karyotypes with 0-6 supernumerary marker/ring chromosomes and review of previously reported cases with two or more markers.

A 7-month-old boy with developmental delay and congenital abnormalities and a 58-year-old man with mental retardation, impaired speech, and … ed to consistently have euchromatin, followed by 15, while 22 and 5 markers were mostly centromeric heterochromatin. The elastin gene probe that maps to 7q11.23, SNRPN gene that maps to 15q11.2, and TUPLE gene that maps to 22q11.2 did not give a signal on the markers. As expected for a majority of ring chromosomes, the pan telomere probe did not hybridize to any …

Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair.

Ataxia telangiectasia (ATM) mutated and Artemis, the proteins defective in ataxia telangiectasia and a class of Radiosensitive-Severe Combined Immunodeficiency (RS-SCID), respectively, function in the repair of DNA double strand breaks (DSBs), which arise in heterochromatic DNA (HC-DSBs) following exposure to ionizing radiation (IR). Here, we examine whether they have protective roles against oxidative damage induced and/or endogenously induced DSBs. We show that DSBs generated following acute exposure of G0/G1 cells to the oxidative damaging agent, tert-butyl hydroperoxide (TBH), are repaired

High interferon response signatures in SLE patient leukocytes are associated with increased transposable element expression in gene introns and intergenic regions.

BACKGROUND: Systemic lupus erythematosus (SLE) is a spontaneous systemic auto-immune condition for which the inciting factors and genetic ba … Es were also observed at intergenic sites distant from annotated genes, perhaps due to weakening of heterochromatin integrity. CONCLUSIONS: Here we describe a strong association between increased TE expression and an ISG-based gene network signature in multiple types of leukocytes centrally involved in SLE pathogenesis. The subset of SLE patients with higher ISG …

Detection of chromosome aberrations in 17 054 individuals with fertility problems and their subsequent assisted reproductive technology treatments in Central China.

STUDY QUESTION: How do the types and frequency of chromosome aberrations in couples in central China affect fertility and ART treatment? SU … 9% ± 2.14%, P = 0.001), especially in men with polymorphisms on Chromosome 9 (enlarged Chromosome 9 heterochromatin [9qh+]: 4.48% ± 2.22% vs 5.59% ± 2.14%, P = 0.006; pericentric inversion of Chromosome 9 [inv(9)]: 5.09% ± 3.11% vs 5.59% ± 2.14%, P = 0.008). ART treatment was successful in 36.00% of couples affected by chromosome aberrations. However, couples aff …

The expanding phenotypes of cohesinopathies: one ring to rule them all!

Preservation and development of life depend on the adequate segregation of sister chromatids during mitosis and meiosis. This process is ens … ivated Cyclic Nucleotide Gated Potassium and Sodium Channel 4;p HDAC8: Histone deacetylases 8; HP1: Heterochromatin Protein 1; ICC: Interstitial Cells of Cajal; ICC-MP: Myenteric Plexus Interstitial cells of Cajal; ICC-DMP: Deep Muscular Plexus Interstitial cells of Cajal; If: Pacemaker Funny Current; IP3: Inositol trisphosphate; JNK: C-Jun N-Terminal Kinase; LDS …

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

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… DNA damage induces heterochromatin loosening and the change of heterochromatin structure is associated with KMT7 (SET7/9)-mediated KMT1A methylation and decreased KMT1 activity 333 . … However, the recruitment of repair factors is slower in dense heterochromatin than in euchromatin, and the DNA repair process is less efficient in heterochromatin 359 , 361 , 362 . The repair of various types of DNA damage in heterochromatin may require complementary mechanisms 304 . …

Rett and ICF syndromes: methylation moves into medicine.

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Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.

Histone methyltransferases (HMTs) and histone demethylases (HDMs) are critical enzymes that regulate chromatin dynamics and gene expression through the addition and removal of methyl groups on histone proteins. HMTs, such as PRC2 and SETD2, are involved in the trimethylation of histone H3 at lysine 27 and lysine 36, influencing gene silencing and activation. Dysregulation of these enzymes often leads to abnormal gene expression and contributes to tumorigenesis. In contrast, HDMs including KDM7A and KDM2A reverse these methylation marks, and their dysfunction can drive disease progression. In c

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… SUV4-20H2 is involved in maintaining heterochromatin stability and regulating transcriptional silencing. … SETDB2 is an HMT specifically targeting H3K9me3, contributing to transcriptional repression and heterochromatin formation. …

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… In humans, heterochromatin stability correlates positively with healthy aging in long‐lived individuals (LLIs) [ 45 ]. … G., et al., “Effect of Heterochromatin Stability on Intestinal Stem Cell Aging in Drosophila,” Mechanisms of Ageing and Development 173 (2018): 50–60. 35. …

Solitary plasmacytoma in the maxillary sinus: 10-year follow-up.

Solitary plasmacytoma (SP) is an uncommon form of plasma cell neoplasm occurring intraosseously or in soft tissue and presents as a single mass of monoclonal plasma cells. SP in the maxillary sinus is rare and can be misdiagnosed as other maxillary sinus tumors. The essential examinations in patients with the initial diagnosis of plasmacytoma are bone marrow biopsy, serum and urine electrophoresis, and kappa/lambda ratio (κ:λ ratio) to rule out multiple myeloma (MM). Herein, a rare case of SP in the maxillary sinus treated by surgery and localized radiation is reported. At the 10-year follow-u

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… Plasma cells had enlarged nuclei, high nucleus-to-cytoplasm ratio, and typically “clock face” heterochromatin arrangement.( Fig. 3 ) Biopsy specimens were stained by kappa lambda (κ:λ) light chain monoclonal antibodies, CD45, S-100, UCHL-1, L26, and CD3. … Cartwheel or clock face is the traditional description for the typical heterochromatin arrangement of plasma cells. Different stages of mitosis also can be observed in histopathological examination. …

Concept of natural genome reconstruction.Part 5. Analysis of changes in the lifespan of old animals after reinfusion of bone marrow cells derived from old animals and treated with hDNAgr in combination with recombinant human angiogenin.

Two series of tests were performed, on mice and rats, to assess the lifespan of old animals reinfused with bone marrow cells from old animals treated with fragmented human DNA (hDNAgr), recombinant human angiogenin, and both preparations together. Animals reinfused with untreated bone marrow cells from old animals or bone marrow cells from young animals were used as comparison groups. Using both outbred mice and CBA/Lac mice, no significant increase in the lifespan of animals reinfused with bone marrow cells treated with the hDNAgr was found compared with the group of mice reinfused with untre

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… The numerous agingassociated diseases are linked to telomeric heterochromatin attrition (Rossiello et al., 2022). … It also indicated that terminal reduction of telomeric heterochromatin had occurred, and telomeres had reached a critical length. …

JAK inhibition in PD-1 immunotherapy and tumor microenvironment.

Targeting the programmed cell death 1 (PD-1)/PD-L1 axis has revolutionized cancer therapy; however, the durability of clinical responses is frequently compromised by chronic inflammation and an immunosuppressive tumor microenvironment (TME). The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway serves as a central intracellular node integrating cytokine signals that drive these resistance mechanisms. While physiological JAK/STAT signaling is essential for antitumor immunity, its persistent aberrant activation promotes malignant progression, upregulates

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… Moreover, unphosphorylated STATs associate with heterochromatin protein-1 (HP1), enhancing to heterochromatin stability. Activation of STATs can displace HP1, changing chromatin organization and gene regulation ( 23 ). … Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability . Nat Cell Biol . ( 2008 ) 10 : 489–96 . doi: 10.1038/ncb1713 , PMID: 18344984 PMC3083919 25 Ogawa H Ishiguro K-I Gaubatz S Livingston DM Nakatani Y . …

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies.

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem-aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of

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… Another unique phenotype of senescent cells is the formation of senescence-associated heterochromatin foci (SAHF), which are specialized regions of facultative heterochromatin that reduce the expression of genes promoting proliferation [ 38 ]. … CRISPR/Cas9-mediated inhibition of SIRT3 resulted in impaired nuclear integrity, loss of heterochromatin, and the accelerated aging of MSCs. SIRT3 was also shown to interact with nuclear envelope proteins and proteins associated with heterochromatin. …

Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management.

The emergence of epigenetic mechanisms as key regulators of gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, epigenetic aberrations have emerged as critical processes that disrupt cellular machinery and homeostasis. Recent discoveries have already translated into successful clinical trials and improved patient care, with several agents approved for hematologic disease and others undergoing study. As the field matures, substantial challenges persist that will require resolution.

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… The genome is organized into relaxed euchromatin and condensed heterochromatin, and DNA is interlaced among histones, which are in turn post-translationally altered to enable or disable transcription. … H3K4me1). 28 Nucleosome positioning represents an additional contributory layer, and is determined by the intrinsic binding affinity of the DNA sequence, competitive binding of surrounding proteins, and translocation activity by adenosine triphosphate-dependent remodeling complexes. 29 Conversely, heterochromatin …

Control of Breast Cancer Pathogenesis by Histone Methylation and the Hairless Histone Demethylase.

Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors, and prognoses. Although traditionally seen as a genetic disease, breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as DNA methyltransferases and histone-modifying enzymes, play essential roles in gene regulation and cancer development. Dysregulation of epigenetic regulator activity has been causally linked with breast cancer pathogenesis. Hairless (HR) encodes a 130-kDa transcription factor that is essential for development and tissue

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… H3K9me1, for example, is found to be associated with both actively transcribed and repressed genes ( 7 , 31 ); whereas H3K9me2 and H3K9me3 are often associated with transcriptional repression or heterochromatin ( 13 , 31 , 34 ). … Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity . Cell. 2012 ; 150 ( 5 ): 948 - 960 . 22939622 10.1016/j.cell.2012.06.048 44. Cloos PA , Christensen J , Agger K , et al. …

YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.

BackgroundYTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells.MethodsRNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We

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… Furthermore, YTHDC1 binds to METTL3 and facilitates METTL3 binding to chromatin in embryonic stem cells, maintaining heterochromatin integrity during mammalian development [ 17 ]. … METTL3 regulates heterochromatin in mouse embryonic stem cells Nature 2021 591 7849 317 321 10.1038/s41586-021-03210-1 33505026 18 Liu Z. Wang T. She Y. …

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV-) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the mo

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… KDM5C inactivation is associated with failed heterochromatin assembly and genome instability, a mechanism that could be exploited by the virus for malignant transformation [ 31 ]. … Human SirT1 Interacts with Histone H1 and Promotes Formation of Facultative Heterochromatin Mol. Cell 2004 16 93 105 10.1016/j.molcel.2004.08.031 15469825 74. Allison S. Jiang M. Milner J. …

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

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… Methylation of histone H3 lysine 4 (H3K4me), H3K36me and H3K79me leads to transcriptional activation, whereas methylation of H3K9me, H3K27me3 and H4K20me leads to transcriptional repression via modification of euchromatin (open chromatin; less condensed chromatin) to heterochromatin (highly condensed … In contrast to heterochromatin, RNA polymerase II (RNAPII) can initiate the gene expression process in euchromatin. The polycomb repressive complex 2 (PRC2; a multi-subunit protein complex) catalyzes tri-methylation of H3K27 to H3K27me3 to regulate the development of multicellular organisms ( 28 ). …

Sp140L функционирует как фактор ограничения герпесвируса, подавляющий вирусную транскрипцию и активирующий интерферонально-стимулированные гены.

Герпесвирусы, включая вирус Эпштейн-Барр (ЭБВ), - человеческий онкогенный вирус и важнейший пусковой механизм множественного склероза, - должны обходить механизмы ДНК-разведки, чтобы установить пожизненную скрытую инфекцию. Поэтому герпесвирусы кодируют вирусные белки, чтобы разрушить ключевые факторы, связанные с зондированием ДНК и вирусным ограничением. Первый вирусный белок латентности, выраженный EBNA-LP, крайне важен для преобразования наивных клеток B и установления вирусного генного экспрессии, однако его роль в уклонении от защиты хостов остается неясной. Используя одноклеточную после

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… Speckled proteins Sp100, Sp110 ( 81 ), and Sp140 ( 86 , 87 ) also associate on cellular chromatin at gene promoters, for instance, Sp100A at ISGs ( 64 ), with Sp140 localizing to sites enriched in H3K27me3 to maintain heterochromatin ( 86 , 87 ). … Multimerization of Sp100 and Sp140L along the viral genome could block transcription either directly or by recruiting repressors to promote heterochromatinization of the viral genome. …