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Epigenetic regulation of histone methyltransferase SUV39H1 on the expression of recombinant protein in CHO cells.

Histone methylation-mediated epigenetic modification significantly influences gene transcription and expression regulation. This study examined the effects of histone 3 lysine 9 trimethylation (H3K9me3) methyltransferase SUV39H1 and its specific inhibitor chaetocin on recombinant protein expression in Chinese hamster ovary (CHO) cells. Results indicated that stable SUV39H1-knockdown CHO cells exhibited reduced H3K9me3 levels while showing increased expression of recombinant adalimumab (rADM) and human serum albumin (rHSA) by approximately 45% and 136%, respectively. Furthermore, treatment with

Histone acetyltransferase KAT6A contributes to colon cancer malignant progression by inhibiting ferroptosis.

BACKGROUND: Colon cancer (CC) is a malignant cancer with high incidence and poor prognosis.Ferroptosis could induce iron-dependent accumulation of lipid peroxidation and oxidative death of cancer cells. This work aimed to elucidate the role of KAT6A, a lysine acetyltransferase, in CC development. METHODS: We collected tumor and paired non-tumor samples from patients with CC and analyzed the RNA and protein level of KAT6A using quantitative real-time PCR and immunohistochemistry (IHC) staining. We conducted KAT6A knockdown in CC cells and determined cell proliferation and ferroptosis. Cell pro

Detecting the distribution patterns of histone lactylation in the mouse testis at different developmental stages.

Lactate is a key glycolytic metabolite that serves as an energy substance and signaling molecule. Lactylation, a recently characterized posttranslational modification (PTM), has been identified in histone and nonhistone proteins. Compelling evidence suggests that this lactate-related epigenetic modification potently regulates gene expression under physiological and pathological conditions. However, the distribution of this histone modification in the testis remains largely unknown. In this study, we investigated the expression dynamics of histone acetyltransferases (HATs), histone deacetylases

ISWI is an Intrinsically Dynamic Nucleosome Remodeler That Induces Large-scale Histone Dynamics.

The chromatin remodeler ISWI plays a crucial role in the maintenance of the dynamic chromatin landscape through its ability to alter nucleosome spacing. Nucleosome remodeling by ISWI involves the translocation of DNA over the histone octamer surface, without disassembly of the nucleosome. Despite the enormous progress in the structural characterization of this process in recent years, it remains unclear to what extent conformational changes in the histone proteins play a role in remodeling. In addition, the conformation and dynamics of regulatory NTR and NegC domains within the remodeler have

Nonchromatin regulatory functions of the histone variant H2A.B in SWI/SNF genomic deposition.

The replacement of canonical histones with their variant forms enables the dynamic and context-dependent regulation of the mammalian genome. Histone variants also play key roles in various pathological processes including malignancies. Among these, the aberrant expression of the testis-specific histone variant H2A.B contributes to the pathogenesis of Hodgkin lymphoma. The multifunctionality of histone variants is regulated by their posttranslational modifications (PTMs). However, the PTMs of H2A.B and their functional implications are unknown. Here, we demonstrate that the Amino terminus of H2…

Insights into histone deacetylase inhibitors-induced cell death in cancer cell lines.

Histone deacetylase inhibitors (HDACis) induce cell death in many chemoresistant cancer models, suggesting their potential as alternative treatments for these malignancies. However, their efficacy in solid tumors remains limited. Therefore, understanding the molecular mechanisms underlying HDACi-induced cell death is essential for developing targeted activators of these pathways, enabling the selective elimination of chemoresistant cancer cells while minimizing the widespread transcriptional effects of HDACis. In this study, we investigated HDACi-induced cell death across models of different c

Hyperagonism of a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule.

1,25-Dihydroxyvitamin D (1,25D) analogs engage the vitamin D receptor (VDR) and can exert anticancer and immunomodulatory effects. Although tumors often resist 1,25D monotherapy, combining VDR agonism with histone deacetylase inhibitors (HDACi) restores anticancer efficacy. Here, we present AC-340, a novel bifunctional molecule that incorporates HDACi into a VDR agonist backbone. Besides its robust bifunctionality in vitro in multiple melanoma models, RNaseq analysis of B16-F10 mouse melanoma cells revealed that AC-340 superinduces the expression of a broad array of VDR target genes. Comparati

Histone Deacetylase 2 in Alzheimer's Disease: A Comprehensive Molecular Blueprint for Therapeutic Targeting.

Alzheimer's disease (AD), which is known for causing cognitive decline and significant synaptic dysfunction, continues to pose a significant barrier to good health among the aging population worldwide. While there remain major knowledge gaps in the exact molecular framework of this complex and devastating disease, emerging evidence strongly implicates epigenetic dysregulation as having a major influence on the complexity of the various pathological processes, driving this debilitating disease. This comprehensive review meticulously delves into the critical and multifaceted role of histone deac

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.

Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identify that chemotherapy-induced PRDM9 upregulation promotes metabolic re

Histone demethylase LSD1 regulates lipid homeostasis during Cryptococcus neoformans infection.

An opportunistic fungal pathogen, Cryptococcus neoformans, causes cryptococcal meningitis and is frequently associated with high mortality in immunocompromised individuals. The formation of metabolically altered lipid-rich foamy macrophages is a successful strategy used by various intracellular pathogens to secure a nutrient source and niche within the host. Herein, we elucidate the involvement of macroautophagy, specifically lipophagy, in lipid dysregulation during C. neoformans infection. C. neoformans driven activation of WNT-signaling leads to an aberrant lipid accumulation in host macroph

The histone demethylase KDM6B links obstructive sleep apnea to idiopathic pulmonary fibrosis.

Obstructive sleep apnea (OSA) is increasingly recognized for its link to idiopathic pulmonary fibrosis (IPF), though the underlying mechanisms remain poorly understood. Histone lysine demethylase 6B (KDM6B) may either prevent or promote organ fibrosis, but its specific role in IPF is yet to be clarified. This study aimed to investigate the function and mechanisms of KDM6B in IPF and the exacerbating effects of OSA. We assessed KDM6B levels in lung tissues from IPF patients, IPF mouse models, and a dual-hit model combining OSA-associated intermittent hypoxia (IH) with bleomycin (BLM) or TGF-β1.

Histone phosphorylation analysis of two main TCM syndromes of chronic fatigue syndrome.

OBJECTIVE: This study aimed to investigate differences in protein expression, protein function, and epigenetic modifications related to histone phosphorylation in peripheral blood mononuclear cells among patients with chronic fatigue syndrome (CFS) presenting two common Traditional Chinese Medicine (TCM) syndrome types compared with healthy controls. METHODS: Three groups of participants were selected from the Medical Examination Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2024 and December 2024. The first group consisted of 10 CFS

Characteristic analysis of adverse reactions of histone deacetylase inhibitors based on WHO-VigiAccess.

BACKGROUND: This study assessed the adverse drug reactions (ADRs) associated with HDAC inhibitors using the VigiAccess database maintained by the World Health Organization (WHO). Furthermore, it compared the ADR profiles of three different drugs to identify the one with the lowest individualized risk for patients. MATERIALS AND METHODS: Data on adverse events of HDAC Inhibitors was retrieved from WHO-VigiAccess on 6 January 2025. We obtained data on age, gender, reporting year, and continent. Descriptive data related were calculated using Excel 2021. In this study, we used Excel software to a

Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis.

Psoriasis involves complex epigenetic alterations, but detailed studies on histone methyltransferases and their role in disease progression are limited. We conducted a comprehensive analysis of nearly 300 transcriptomes, focusing mainly on differential expression of protein isoform-coding transcripts within the SET domain family of histone methyltransferases. Consistent with previous findings, EZH2 transcripts showed increased expression in lesional skin, indicating altered H3K27 methylation that may enhance gene silencing, promoting keratinocyte proliferation and inflammatory responses. In th

Assessment of the Histone Mark-based Epigenomic Landscape in Human Myometrium at Term Pregnancy.

The myometrium plays a critical role during pregnancy as it is responsible for both the structural integrity of the uterus and force generation at term. Emerging studies in mice indicate a dynamic change of the myometrial epigenome and transcriptome during pregnancy to ready the contractile machinery for parturition. However, the regulatory systems underlying myometrial gene expression patterns throughout gestation remain largely unknown. Here we investigated human term pregnant nonlabor myometrial biopsies for transcriptome, enhancer histone mark cistrome, and chromatin conformation pattern m

Assessment of the histone mark-based epigenomic landscape in human myometrium at term pregnancy.

The myometrium plays a critical role during pregnancy as it is responsible for both the structural integrity of the uterus and force generation at term. Emerging studies in mice indicate a dynamic change of the myometrial epigenome and transcriptome during pregnancy to ready the contractile machinery for parturition. However, the regulatory systems underlying myometrial gene expression patterns throughout gestation remain largely unknown. Here, we investigated human term pregnant nonlabor myometrial biopsies for transcriptome, enhancer histone mark cistrome, and chromatin conformation pattern

DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite treatment advances, the survival rates of high-risk NB patients remain low. This highlights the urgent need for a deeper understanding of the molecular mechanisms driving NB progression to support the development of new therapeutic strategies. In this study, we demonstrated that the reduced levels of DNAJC12, a protein involved in metabolic regulation, are associated with poor prognosis in NB patients. Our data indicate that low DNAJC12 expression activates glycolysis in NB cells, leading to increased lactic ac

Histone deacetylase 6 inhibitors in Alzheimer's disease therapy: structure design and challenges.

Recently, histone deacetylases 6 (HDAC6) has been extensively studied for involvement in pathogenesis of central nervous system (CNS) diseases, especially for Alzheimer's disease (AD). A lot of literatures have disclosed that HDAC6 inhibitors (HDAC6is) are effective and promising in AD treatment. Though many HDAC6is were reported, only a handful of them displayed appropriate in vivo activities in models of neurological diseases. BBB permeability and off-target toxicity are the major obstacle and challenge for the development of available HDAC6is. In this review, we summarized recent brain-perm

ACLY promotes NK cell effector function by regulating glycolysis and histone acetylation.

Natural killer (NK) cells are innate immune lymphocytes important for host viral and tumor immunity. We investigated the requirement for ATP citrate lyase (ACLY) in NK cell function using an inducible genetic mouse model. ACLY regulates the citrate-malate shuttle, generating cytosolic acetyl-coenzyme A that is primarily used for acetylation or lipid synthesis. ACLY-deficient NK cells upon IL-15 activation exhibited significant defects in glycolysis, proliferation, cytokine production, and cytotoxicity, without decreased intracellular lipids. Notably, ACLY deficiency specifically resulted in re

Potential of histone deacetylase 6 inhibitors in alleviating chemotherapy-induced peripheral neuropathy.

BackgroundHistone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates the acetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development of tumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of

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… INTRODUCTION Histone deacetylase (HDAC) is an enzyme that hydrolyzes the acetyl-L-lysine side chain in the N-terminal region of histones. Among the various HDAC subtypes, histone deacetylase 6 (HDAC6) is unique due to its dual catalytic domains and classification in the IIb group [ 1 ]. … CKD-011, an HDAC6 inhibitor, was added at different concentrations, and the expression of acetylated tubulin, total tubulin, ubiquitin, acetylated histone H3, and total histone H3 was confirmed using immunoblotting. HDAC6: histone deacetylase 6. …