A5036890817- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Ubiquitin and proteasome pathways
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- T-cell and Retrovirus Studies
- Metastasis and carcinoma case studies
- Microtubule and mitosis dynamics
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- FOXO transcription factor regulation
- HIV Research and Treatment
- DNA Repair Mechanisms
- interferon and immune responses
- Viral Infections and Immunology Research
Tianjin Medical University
2015-2025
BGI Research
2024
Tianjin Medical University General Hospital
2022-2024
Botswana Geoscience Institute
2024
University of Chinese Academy of Sciences
2024
Tianjin Medical University Cancer Institute and Hospital
2021
Peking University
2010-2011
Nankai University
2004-2007
It is well-documented that the methylation of histone H3 lysine 4 (H3K4) and H3K9 are mutually exclusive, an epigenetic phenomenon conserved from yeast to humans. How this opposed modification accomplished coordinated in mammalian cells poorly understood. Here we report trimethyl demethylase JMJD2B integral component H3K4-specific methyltransferase, mixed-lineage leukemia (MLL) 2 complex. We show JMJD2B/MLL2 complex copurified with estrogen receptor α (ERα) required for ERα-regulated...
Significance DNA double-strand breaks are generally repaired in the context of highly organized chromatin. However, how epigenetic mechanisms involved maintenance genetic fidelity remains poorly understood. Here we report that lysine-specific histone demethylase 5B (KDM5B), a well-defined transcriptional repressor, promotes break signaling and is required for efficient repairs. We demonstrated KDM5B, doing so, functions to orchestrate checkpoint activation cell survival after damage. Our...
Genome-wide association studies have generated over thousands of susceptibility loci for many human complex traits, and yet most these associations the true causal variants remain unknown. Tissue/cell type-specific prediction prioritization non-coding regulatory will facilitate identification underlying pathogenic mechanisms particular diseases traits. By leveraging recent large-scale functional genomics/epigenomics data, we develop an intuitive web server, GWAS4D...
Whether transcriptional regulators are functionally involved in mitosis is a fundamental question cell biology. Here we report that the RNF20/40 complex, major ubiquitin ligase catalysing histone H2B monoubiquitination, interacts with motor protein Eg5 during and participates spindle assembly. We show complex monoubiquitinates stabilizes Eg5. Loss of results assembly defects, cycle arrest apoptosis. Consistently, depletion either or suppresses breast cancer vivo. Significantly, concurrently...
As a crucial element of proteolysis targeting chimeras (PROTACs), the choice E3 ubiquitin ligase significantly influences degradation efficacy and selectivity. However, available arsenal ligases for PROTAC development remains underexplored, severely limiting scope targeted protein degradation. In this study, we identify non-inhibitory aptamer ZYG11B, substrate receptor Cullin 2-RING complex, as an warhead This aptamer-based platform, termed ZATAC, is facilely produced through bioorthogonal...
Competing endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number associated with ceRNA's using Geuvaids RNA-seq data for 462 individuals from 1000 Genomes Project. We call these loci competing quantitative trait or 'cerQTL', found them were unexplored...
Transcription activation by estrogen receptor (ER) is rapid and dynamic. How the prompt precise ER response established maintained still not fully understood. Here, we report that two boundary elements surrounding well defined ERα target TFF1 locus are occupied CCCTC-binding factor (CTCF). These separated 40 kb but cluster in nuclear space depending on CTCF independent of transcription. In contrast, non-responsive breast cancer cells, spatial proximity these lost entire instead displays a...
The advances of large-scale genomics studies have enabled compilation cell type-specific, genome-wide DNA functional elements at high resolution. With the growing volume annotation data and sequencing variants, existing variant algorithms lack efficiency scalability to process big genomic data, particularly when annotating whole-genome variants against a huge database with billions features. Here, we develop VarNote rapidly annotate genome-scale in large complex resources. Equipped novel...
Ferroptosis is an iron-catalyzed form of regulated cell death that results from the accumulation lipid peroxidation products and reactive oxygen species to a lethal content. However, transcriptional regulation ferroptosis not well understood. Sorafenib, standard drug for hepatocellular carcinoma (HCC), induces in HCC cells. In this study, we conducted CRISPR-Cas9 library screening targeting epigenetic factors identified coactivator-associated arginine methyltransferase 1 (CARM1) as critical...
Abstract Alternative polyadenylation can occur in introns, termed intronic (IPA), has been implicated diverse biological processes and diseases, as it produce noncoding transcripts or with truncated coding regions. However, a reliable method is required to accurately characterize IPA. Here, we propose computational called InPACT, which allows for the precise characterization of IPA from conventional RNA-seq data. InPACT successfully identifies numerous previously unannotated human cells,...
Abstract Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Understanding the dysregulated epigenetics governing LUAD progression is pivotal for identifying therapeutic targets. CBX4, chromobox protein, reported to be upregulated in LUAD. This study highlights dual impact CBX4 on proliferation and metastasis through series rigorous vitro vivo experiments. Further investigation into underlying mechanism high-throughput ChIP-seq RNA-seq reveals that...
Histone methyltransferase DOT1L is implicated in various biological processes including cell proliferation, differentiation and embryogenesis. Gene ablation of Dot1l results embryonic lethality cardiovascular defects decreased vasculature. However, how might contribute to the development vasculature not clear. Here, we report that required for angiogenesis. We demonstrated silencing human umbilical vein endothelial cells (HUVECs) leads viability, migration, tube formation, capillary sprout...
The initiation and transduction of DNA damage response (DDR) occur in the context chromatin, modifications as well structure chromatin are crucial for DDR signaling. How profound alterations confined to lesions by epigenetic factors remains largely unclear. Here, we discover that JMJD6, a Jumonji C domain-containing protein, is recruited double-strand breaks (DSBs) after microirradiation. JMJD6 controls spreading histone ubiquitination, subsequent accumulation repair proteins transcriptional...
Abstract Polycomb group proteins are often dysregulated in cancer, leading to disruption of epigenetic landscapes and acquisition cancer hallmarks. Chromobox 8 (CBX8) is a core component canonical polycomb repressive complex 1; however, its role transcriptional regulation ovarian carcinoma progression has not been extensively investigated. In this study, we find that CBX8 upregulated cancer. Overexpression knockdown approaches show facilitates the growth migration CAOV3, A2780, SKOV3 cells...