BACKGROUND: Various epigenetic regulations systematically govern gene expression in cells involving various biological processes. Dysregulation of the epigenome leads to aberrant transcriptional programs and subsequently results in diseases, such as cancer. Therefore, comprehensive profiling epigenomics is essential for exploring the mechanisms underlying gene expression regulation during development and disease.
METHODS: In this study, we developed single-cell chromatin proteins and accessibility tagmentation (scCPA-Tag), a multi-modal single-cell epigenetic profile capturing technique based on barcoded Tn5 transposases and a droplet microfluidics platform. scCPA-Tag enables the simultaneous capture of DNA profiles of histone modification and chromatin accessibility in the same cell.
RESULTS: By applying scCPA-Tag to K562 cells and a hepatocellular carcinoma (HCC) sample, we found that the silence of several chromatin-accessible genes can be attributed to lysine-27-trimethylation of the histone H3 tail (H3K27me3) modification. We characterized the epigenetic features of the tumour cells and different immune cell types in the HCC tumour tissue by scCPA-Tag. Besides, a tumour cell subtype (C2) with more aggressive features was identified and characterized by high chromatin accessibility and a lower abundance of H3K27me3 on tumour-promoting genes.
CONCLUSIONS: Our multi-modal scCPA-Tag provides a comprehensive approach for exploring the epigenetic landscapes of heterogeneous cell types and revealing the mechanisms of gene expression regulation during developmental and pathological processes at the single-cell level.
CONCLUSIONS: scCPA-Tag offers a highly efficient and high throughput technique to simultaneously profile histone modification and chromatin accessibility within a single cell. scCPA-Tag enables to uncover multiple epigenetic modification features of cellular compositions within tumor tissues. scCPA-Tag facilitates the exploration of the epigenetic landscapes of heterogeneous cell types and provides the mechanisms governing gene expression regulation.

慢性鼻窦炎（CRS）是一种常见的慢性炎性疾病，由于其存在高度异质性，早期准确的临床诊断和治疗对控制CRS的病情至关重要。多种组学技术可以全面系统地分析CRS患者DNA、RNA、蛋白质的差异表达及生物学功能，有利于深入研究CRS内在机制，为实现CRS的精准诊疗提供了可能。本文分别概述基因组学、表观基因组学、转录组学、蛋白质组学和代谢组学等各类组学方法在CRS中的研究进展，对既往研究数据进行归纳整合和分析，阐明多组学技术在推动CRS精准诊疗中的重要作用，并为CRS的精准诊疗提供新的方向。.

Cleavage Under Targets and Tagmentation (CUT&Tag) provides high-resolution sequencing libraries for profiling diverse chromatin components. This protocol details the steps to generate CUT&Tag libraries from fresh or frozen tissues. This CUT&Tag workflow has nine main steps: isolation of nuclei from tissues, binding of nuclei to Concanavalin A-coated beads, binding of the primary antibody, binding of the secondary antibody, binding pA-Tn5 adapter complex, tagmentation, DNA extraction, PCR, and post-PCR cleanup and size selection. This protocol enabled us to generate and sequence CUT&Tag libraries across a broad range of fresh and frozen tissue types.

BACKGROUND: Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients.
METHODS: We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate.
RESULTS: As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%).
CONCLUSIONS: The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies.
BACKGROUND: This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

BACKGROUND: Winter wheat undergoes vernalization, a process activated by prolonged exposure to low temperatures. During this phase, flowering signals are generated and transported to the apical meristems, stimulating the transition to the inflorescence meristem while inhibiting tiller bud elongation. Although some vernalization genes have been identified, the key cis-regulatory elements and precise mechanisms governing this process in wheat remain largely unknown.
RESULTS: In this study, we construct extensive epigenomic and transcriptomic profiling across multiple tissues-leaf, axillary bud, and shoot apex-during the vernalization of winter wheat. Epigenetic modifications play a crucial role in eliciting tissue-specific responses and sub-genome-divergent expressions during vernalization. Notably, we observe that H3K27me3 primarily regulates vernalization-induced genes and has limited influence on vernalization-repressed genes. The integration of these datasets enables the identification of 10,600 putative vernalization-related regulatory elements including distal accessible chromatin regions (ACRs) situated 30Kb upstream of VRN3, contributing to the construction of a comprehensive regulatory network. Furthermore, we discover that TaSPL7/15, integral components of the aging-related flowering pathway, interact with the VRN1 promoter and VRN3 distal regulatory elements. These interactions finely regulate their expressions, consequently impacting the vernalization process and flowering.
CONCLUSIONS: Our study offers critical insights into wheat vernalization\'s epigenomic dynamics and identifies the putative regulatory elements crucial for developing wheat germplasm with varied vernalization characteristics. It also establishes a vernalization-related transcriptional network, and uncovers that TaSPL7/15 from the aging pathway participates in vernalization by directly binding to the VRN1 promoter and VRN3 distal regulatory elements.

Regulating gene expression in plant development and environmental responses is vital for mitigating the effects of climate change on crop growth and productivity. The eukaryotic genome largely shows the canonical B-DNA structure that is organized into nucleosomes with histone modifications shaping the epigenome. Nuclear proteins and RNA interactions influence chromatin conformations and dynamically modulate gene activity. Non-B DNA conformations and their transitions introduce novel aspects to gene expression modulation, particularly in response to environmental shifts. We explore the current understanding of non-B DNA structures in plant genomes, their interplay with epigenomics and gene expression, and advances in methods for their mapping and characterization. The exploration of so far uncharacterized non-B DNA structures remains an intriguing area in plant chromatin research and offers insights into their potential role in gene regulation.

Colorectal cancer is one of the most common cancers worldwide. Lymph node metastasis is an important marker of colorectal cancer progression and plays a key role in the evaluation of patient prognosis. Accurate preoperative assessment of lymph node metastasis is crucial for devising appropriate treatment plans. However, current clinical imaging methods have limitations in many aspects. Therefore, the discovery of a method for accurately predicting lymph node metastasis is crucial clinical decision-making. DNA methylation is a common epigenetic modification that can regulate gene expression, which also has an important impact on the development of colorectal cancer. It is considered to be a promising biomarker with good specificity and stability and has promising application in predicting lymph node metastasis in patients with colorectal cancer. This article reviews the characteristics and limitations of currently available methods for predicting lymph node metastasis in patients with colorectal cancer and discusses the role of DNA methylation as a biomarker.

Objective: Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data. Methods: Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseⅠ, the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseⅡ, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results: The three-stage analytic strategy identified a methylation site (cg16126280EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95%CI:1.000 7-1.001 5,P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280EBF1 was completely opposite in younger patients (HR=0.550 5, 95%CI: 0.383 8-0.789 6, P=0.001) and older patients (HR=2.166 5, 95%CI: 1.285 2-3.652 2, P=0.004). Conclusions: The DNA methylation site cg16126280EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.
目的： 基于表观基因组数据，探索乳腺癌预后基因-年龄交互作用。 方法： 利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）多个独立乳腺癌表观基因组数据集，进行DNA甲基化的差异表达分析。采用错误发现率（FDR）法进行多重校正，保留q-FDR≤0.05的差异表达甲基化位点。应用三阶段分析策略，采用多因素Cox比例风险回归模型检验基因-年龄交互作用。发现阶段使用TCGA-BRCA数据库筛选q-FDR≤0.05的信号。验证阶段Ⅰ使用GSE72245数据验证交互作用，标准为P≤0.05且效应方向一致。验证阶段Ⅱ使用GSE37754和GSE75067数据再次验证信号。通过结合临床指标与交互作用信号构建预后预测模型。 结果： 三阶段分析策略鉴定出一个甲基化位点（cg16126280EBF1），其与年龄存在交互作用，共同影响患者的生存时间（交互作用HR=1.001 1，95%CI：1.000 7~1.001 5，P<0.001）。年龄分层分析显示，cg16126280EBF1的高甲基化效应在乳腺癌年轻患者（HR=0.550 5，95%CI：0.383 8~0.789 6，P=0.001）和老年患者中完全相反（HR=2.166 5，95%CI：1.285 2~3.652 2，P=0.004）。 结论： DNA甲基化位点cg16126280EBF1与年龄存在交互作用，以复杂的关联模式共同影响乳腺癌预后，为年龄特异性靶向药物研发提供了新的人群证据。.

Plants possess diverse cell types and intricate regulatory mechanisms to adapt to the ever-changing environment of nature. Various strategies have been employed to study cell types and their developmental progressions, including single-cell sequencing methods which provide high-dimensional catalogs to address biological concerns. In recent years, single-cell sequencing technologies in transcriptomics, epigenomics, proteomics, metabolomics, and spatial transcriptomics have been increasingly used in plant science to reveal intricate biological relationships at the single-cell level. However, the application of single-cell technologies to plants is more limited due to the challenges posed by cell structure. This review outlines the advancements in single-cell omics technologies, their implications in plant systems, future research applications, and the challenges of single-cell omics in plant systems.

The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants. More recently, genetic and epigenetic genome-wide studies have revealed new pathways in the inflammatory process of gout, including genetic associations with epigenomic modifiers. Epigenome-wide association studies are also implicating epigenomic remodelling in gout, which perhaps regulates the responsiveness of the innate immune system to monosodium urate crystals. Notably, genes implicated in gout GWAS do not include those encoding components of the NLRP3 inflammasome itself, but instead include genes encoding molecules involved in its regulation. Knowledge of the molecular mechanisms underlying gout has advanced through the translation of genetic associations into specific molecular mechanisms. Notable examples include ABCG2, HNF4A, PDZK1, MAF and IL37. Current genetic studies are dominated by participants of European ancestry; however, studies focusing on other population groups are discovering informative population-specific variants associated with gout.