The role of histone H3K36me3 writers, readers and erasers in maintaining genome stability

DNA repair, Journal Year: 2022, Volume and Issue: 119, P. 103407 - 103407

Published: Sept. 16, 2022

Histone Post-Translational Modifications (PTMs) play fundamental roles in mediating DNA-related processes such as transcription, replication and repair. The histone mark H3K36me3 its associated methyltransferase SETD2 (Set2 yeast) are archetypical this regard, performing critical each of these DNA transactions. Here, we present an overview regulation the writers, readers erasers maintaining genome stability through facilitating double-strand break (DSB) repair, checkpoint signalling stress responses. Further, consider how loss H3K36me3, frequently observed a number different cancer types, can be specifically targeted clinic exploiting particular functions.

Language: Английский

---

HPV induced R-loop formation represses innate immune gene expression while activating DNA damage repair pathways

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012454 - e1012454

Published: Aug. 23, 2024

R-loops are trimeric nucleic acid structures that form when an RNA molecule hybridizes with its complementary DNA strand, displacing the opposite strand. These regulate transcription as well replication, but aberrant can form, leading to breaks and genomic instability if unresolved. R-loop levels elevated in many cancers cells maintain high-risk human papillomaviruses. We investigated how distribution function of changed between normal keratinocytes HPV positive derived from a precancerous lesion cervix (CIN I). The associated cellular genes were found be up 10-fold higher than while increases at ALU1 elements increased by 500-fold. presence enhanced resulted altered gene transcription, equal numbers decreased. While no uniform global effects on due detected, several pathways coordinately or decreased expression only cells. This included downregulation innate immune pathway, such DDX58, IL-6, STAT1, IFN-β, NLRP3. All differentially expressed dependent also H3K36me3 modified histones. Genes upregulated those damage repair ATM, ATRX, members Fanconi Anemia pathway. exhibited linkage γH2AX histone marks studies identify potential link regulatory γH2AX/H3K36me3 may contribute regulating important functions for pathogenesis.

Language: Английский

---

NSD3: Advances in cancer therapeutic potential and inhibitors research

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 256, P. 115440 - 115440

Published: May 10, 2023

Language: Английский

---

Disruption of H3K36 methylation provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(2), P. 187 - 198.e7

Published: Jan. 1, 2024

Language: Английский

---

Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(6), P. 2662 - 2697

Published: May 14, 2024

Language: Английский

---

Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 21, 2023

SET domain-containing 2 (SETD2) is a lysine methyltransferase that catalyzes histone H3 lysine36 trimethylation (H3K36me3) and has been revealed to play important roles in the regulation of transcriptional elongation, RNA splicing, DNA damage repair. SETD2 mutations have documented several cancers, including clear cell renal carcinoma (ccRCC). deficiency associated with cancer occurrence progression by regulating autophagy flux, general metabolic activity, replication fork speed. Therefore, considered potential epigenetic therapeutic target subject ongoing research on cancer-related diagnosis treatment. This review presents an overview molecular functions H3K36me3 its relationship ccRCC, providing theoretical basis for subsequent antitumor therapy based or targets.

Language: Английский

---

Sequence-Only Prediction of Super-Enhancers in Human Cell Lines Using Transformer Models

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 172 - 172

Published: Feb. 7, 2025

The study discloses the application of transformer-based deep learning models for task super-enhancers prediction in human tumor cell lines with a specific focus on sequence-only features within studied entities super-enhancer and enhancer elements genome. proposed SE-prediction method included GENA-LM at handling long DNA sequences classification task, distinguishing from enhancers using H3K36me, H3K4me1, H3K4me3 H3K27ac landscape datasets HeLa, HEK293, H2171, Jurkat, K562, MM1S U87 lines. model was fine-tuned relevant sequence data, allowing analysis extended genomic without need epigenetic markers as early approaches. achieved balanced accuracy metrics, surpassing previous like SENet, particularly HEK293 K562 Also, it shown that frequently co-localize marks such H3K27ac. Therefore, attention mechanism provided insights into contributing to SE classification, indicating correlation between mentioned landscapes. These findings support potential transformer use further bioinformatics applications enhancer/super-enhancer characterization gene regulation studies.

Language: Английский

---

Cotton under heat stress: a comprehensive review of molecular breeding, genomics, and multi-omics strategies

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 16

Published: March 18, 2025

Cotton is a vital fiber crop for the global textile industry, but rising temperatures due to climate change threaten its growth, quality and yields. Heat stress disrupts key physiological biochemical processes, affecting carbohydrate metabolism, hormone signaling, calcium gene regulation expression. This review article explores cotton's defense mechanism against heat stress, including epigenetic regulations transgenic approaches, with focus on genome editing tools. Given limitations of traditional breeding, advanced omics technologies such as GWAS, transcriptomics, proteomics, ionomics, metabolomics, phenomics CRISPR-Cas9 offer promising solutions developing heat-resistant cotton varieties. highlights need innovative strategies ensure sustainable production under change.

Language: Английский

---

NSD1 mutation status determines metabolic inhibitor sensitivity in head and neck squamous cell carcinomas by regulating mitochondrial respiration

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Abstract Head and neck squamous cell carcinomas (HNSCCs) are the most common malignant tumors in head region, characterized by a high recurrence rate early metastasis. Despite advances treatment, patient outcomes prognosis remain poor, highlighting urgent need for new therapeutic strategies. Recent research has increasingly focused on targeting glucose metabolism as strategy cancer, revealing multiple promising targets potential drugs. However, metabolic heterogeneity among leads to variable sensitivity inhibitors different patients, limiting their clinical utility. In this study, we employed bioinformatics analysis, experiments, animal models, multi‐omics approaches reveal differences phenotypes HNSCC patients elucidated underlying molecular mechanisms driving these differences. Our findings showed that NSD1 mutation status affects phenotype HNSCC, with wild‐type exhibiting higher mitochondrial respiration mutant showing weaker but enhanced glycolysis. We further demonstrated regulates via epigenetic modulation of TGFB2 / PPARGC1A signaling axis. Additionally, found is more sensitive inhibitors, whereas shows increased glycolysis inhibitors. summary, can epigenetically regulate axis modulate HNSCC. These suggest novel selecting based gene patients. © 2025 The Pathological Society Great Britain Ireland.

Language: Английский

---

Discovery of NSD2 non-histone substrates and design of a super-substrate

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: June 8, 2024

Abstract The human protein lysine methyltransferase NSD2 catalyzes dimethylation at H3K36. It has very important roles in development and disease but many mechanistic features its full spectrum of substrate proteins are unclear. Using peptide SPOT array methylation assays, we investigate the sequence specificity discover strong readout residues between G33 (-3) P38 (+2) on Unexpectedly, observe that amino acid different from natural ones H3K36 preferred some positions. Combining four led to a super-substrate which is methylated much faster by level. Molecular dynamics simulations demonstrate this activity increase caused distinct hyperactive conformations enzyme-peptide complex. To NSD2, conducted proteome wide search for nuclear matching profile discovered 22 substrates NSD2. In studies, identify K1033 ATRX K819 FANCM as sites also their cells. Both these have DNA repair strengthening connection repair.

Language: Английский

---