A5100460281- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Plant Molecular Biology Research
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Genetic Syndromes and Imprinting
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Synthesis and Reactions of Organic Compounds
- Melanoma and MAPK Pathways
- Molecular Biology Techniques and Applications
- Diet and metabolism studies
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Pluripotent Stem Cells Research
Howard Hughes Medical Institute
2012-2025
Boston Children's Hospital
2022-2025
Ministry of Agriculture and Rural Affairs
2023-2025
Zhejiang University
2025
Second Affiliated Hospital of Zhejiang University
2021-2025
University of Hong Kong
2010-2025
Moffitt Cancer Center
2022-2025
Hong Kong University of Science and Technology
2010-2025
Sun Yat-sen University
2024-2025
Guangxi University
2025
The function of human TFIIH-associated Cdk7 in RNA polymerase II (Pol II) transcription and C-terminal domain (CTD) phosphorylation was investigated analogue-sensitive Cdk7(as/as) mutant cells where the kinase can be inhibited without disrupting TFIIH. We show that both Cdk9/PTEFb contribute to Pol CTD Ser5 residues on transcribed genes. is also a major Ser7 at c-fos U snRNA Furthermore, TFIIH recombinant Cdk7-CycH-Mat1 as well Cdk9-CycT1 phosphorylated vitro. Inhibition vivo suppressed...
The Saccharomyces cerevisiae kinase Bur1 is involved in coupling transcription elongation to chromatin modification, but not all important targets the complex are known. Using a chemical genetics strategy wherein was engineered be regulated by specific inhibitor, we found that phosphorylates Spt5 C-terminal repeat domain (CTD) both vivo and isolated complexes vitro. Deletion of CTD or mutation serines targeted reduces recruitment PAF complex, which functions recruit factors modification mRNA...
Abstract Cellular senescence is a well-orchestrated programmed process involved in age-related pathologies, tumor suppression and embryonic development. TGF-β/Smad one of the predominant pathways that regulate damage-induced developmentally senescence. Here we show canonical TGF-β signaling promotes via miR-29-induced loss H4K20me3. Mechanistically, oxidative stress triggers signaling. Activated gives rise to acute accumulation miR-29a miR-29c, both which directly suppress their novel...
Abstract Quaking (QKI) is an alternative splicing factor that can regulate circRNA formation in the progression of epithelial–mesenchymal transition, but mechanism remains unclear. High expression QKI correlated with short survival time, metastasis, and high clinical stage pathology grade hepatocellular carcinoma (HCC). Here we report transcription gene was activated by Yin-Yang 1 (YY1)/p65/p300 complex, which YY1 bound to super-enhancer promoter QKI, p65 combined promoter, p300 served as a...
Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients acceptable safety profile as monotherapy. EED, another PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on 3 (H3K27Me3). Herein we disclose discovery a first-in-class potent,...
Abstract 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues fundamental to understanding its regulatory functions. Here, we systematically profiled whole-genome at single-base resolution for 19 types tissues. We found preferentially decorates bodies and outperforms body 5mC reflecting Approximately one-third peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which deposited...
Abstract Chromatin organization and transcriptional profiles undergo tremendous reordering during senescence. However, uncovering the regulatory mechanisms between chromatin reconstruction gene expression in senescence has been elusive. Here, we depicted landscapes of both accessibility to reveal networks human umbilical vein endothelial cell (HUVEC) found that accessibilities are redistributed Particularly, intergenic was massively shifted with increased regions (IARs) or decreased (DARs),...
Abstract The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and executive action to even pain processing. To decode the cellular circuit organization of such functions, we employed spatially resolved single-cell transcriptome profiling adult mouse PFC. Results revealed PFC has distinct cell-type composition gene-expression patterns relative neighboring cortical areas—with neuronal excitability-regulating genes differently...
Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of cancer, and there no effective treatment other than chemotherapy. Processing precursors 1 (POP1) most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, role POP1 TNBC remains clarified. A series molecular biological experiments vitro vivo clinical correlation analyses were conducted to clarify function regulatory mechanism Here, we identified that significantly associated with poor...
Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple modifications. However, a comprehensive elucidation clinical value various modifications breast is still lacking. This study aimed provide strategy based on modification-related genes for predicting therapy response and survival outcomes patients. Genes thirteen patterns were integrated establishing nine-gene-containing signature-RMscore. Alterations tumor immune microenvironment...
Spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly because of the large numbers starting cells required for current conformation capture approaches. Here, we introduce a low-input tagmentation-based Hi-C (tagHi-C) method to structures hundreds cells. Using tagHi-C, are able map spatiotemporal dynamics structure in ten primary stem, progenitor, and differentiated cell populations from mouse bone marrow. Our results...
The three-dimensional configuration of the chromatin architecture is known to be crucial for alterations in transcriptional network; however, underlying mechanisms epigenetic control senescence-related gene expression by modulating remain unknown. Here, we demonstrate frequent chromosomal compartment switching during mouse embryonic fibroblasts (MEFs) replicative senescence as characterized senescence-inactivated (SIAEs) and -activated enhancers (SAEs) topologically associated domains...
Abstract Orchestrating complex behaviors, such as approaching and consuming food, is critical for survival. In addition to hypothalamus neuronal circuits, the nucleus accumbens (NAc) also controls appetite satiety. However, specific subtypes of NAc that are involved how humoral signals coordinate regulate feeding remain incompletely understood. Here we decipher spatial diversity neuron shell (NAcSh) define a dopamine receptor D1-expressing Serpinb2- expressing subtype controlling food...
Transcript elongation by RNA polymerase II (RNAPII) is accompanied conserved patterns of histone modification. Whereas modifications have established roles in transcription initiation, their functions during are not understood. Mono-ubiquitylation H2B (H2Bub1) plays a key role coordinating co-transcriptional modification promoting site-specific methylation H3. H2Bub1 also regulates gene expression through an unidentified, methylation-independent mechanism. Here we reveal bidirectional...
Glioma, as one of the most aggressive tumors, is hardly cleaned by surgical removal, leading to a low survival rate. m6A an internal modification in RNA and plays important role many kinds cancers. In our study, we detected that level was decreased glioma tissue, which might be caused METTL3 increased FTO levels. We upregulated U251 cells overexpressing <i>METTL3</i>. The results showed high led reduced migration proliferation ability, vice versa. Finally, performed TUNEL assay...
Congenital heart disease (CHD) is the leading non-infectious cause of death in infants. Monozygotic (MZ) twins share nearly all their genetic variants before and after birth. Nevertheless, MZ are sometimes discordant for common complex diseases. The goal this study to identify genomic epigenomic differences between a pair form congenital disease, double outlet right ventricle (DORV). A monoamniotic monozygotic twin DORV were subjected genome-wide sequencing methylation analysis. We...
Plasma cells provide high-affinity antibodies against invading pathogens. Although transcriptional and epigenetic mechanisms have been extensively studied for plasma cell differentiation, how these respond to environmental cues remains largely unexplored. In this study, we show that ascorbic acid (vitamin C), an essential nutrient, is able promote differentiation humoral immune response by enhancing TET2/3-mediated DNA demethylation. Ascorbic treatment during B activation has persistent...
Abstract Tracing cellular dynamic changes across conditions, time, and space is crucial for understanding the molecular mechanisms underlying complex biological systems. However, integrating multi-sample data in a unified flexible way to explore heterogeneity remains major challenge. Here, we present Stereopy, versatile framework modeling dissecting comparative spatiotemporal patterns spatial transcriptomics with interactive visualization. To optimize this framework, have developed three key...
Lysine-specific demethylase 1 (LSD1) is a histone that promotes stemness and cell survival in cancers such as prostate cancer. Most malignancies are adenocarcinomas with luminal differentiation. However, some tumors undergo cellular reprogramming to more lethal subset termed neuroendocrine cancer (NEPC) neuronal The frequency of NEPC increasing since the widespread use potent androgen receptor signaling inhibitors. Currently, there no effective treatments for NEPC. We previously determined...