- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Air Quality and Health Impacts
- T-cell and B-cell Immunology
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- TGF-β signaling in diseases
- Immunotherapy and Immune Responses
- Bone Metabolism and Diseases
- RNA Research and Splicing
- Climate Change and Health Impacts
- Nanoparticles: synthesis and applications
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Health, Environment, Cognitive Aging
- Acute Myeloid Leukemia Research
- Gene expression and cancer classification
Hubei Normal University
2024
National Heart Lung and Blood Institute
2020-2024
National Institutes of Health
2020-2024
Chinese Center For Disease Control and Prevention
2021-2023
Nanjing Medical University
2022-2023
University of Cambridge
2023
Illumina (United Kingdom)
2023
Shanghai Institute of Nutrition and Health
2018-2022
Shanghai Institutes for Biological Sciences
2014-2022
Changzhou Architectural Research Institute Group (China)
2022
Mammalian genomes have multiple enhancers spanning an ultralong distance (>megabases) to modulate important genes, but it is unclear how these coordinate achieve this task. We combine multiplexed CRISPRi screening with machine learning define quantitative enhancer-enhancer interactions. find that the enhancer network has a nested multilayer architecture confers functional robustness of gene expression. Experimental characterization reveals epistasis maintained by three-dimensional...
Abstract Motivation Sequencing-based 3D genome mapping technologies can identify loops formed by interactions between regulatory elements hundreds of kilobases apart. Existing loop-calling tools are mostly restricted to a single data type, with accuracy dependent on predefined resolution contact matrix or called peaks, and have prohibitive hardware costs. Results Here, we introduce cLoops (‘see loops’) address these limitations. is based the clustering algorithm cDBSCAN that directly...
LSH, a SNF2 family DNA helicase, is key regulator of methylation in mammals. How LSH facilitates not well defined. While previous studies with mouse embryonic stem cells (mESc) and fibroblasts (MEFs) derived from Lsh knockout mice have revealed role de novo by Dnmt3a/3b, here we report that contributes to various cell lines primarily promoting DNMT1. We show loss has much bigger effect than DNMT3A DNMT3B. Mechanistically, demonstrate interacts UHRF1 but DNMT1 chromatin association...
Abstract The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, understand the temporospatial regulation expression. In this study, we report Hi-TrAC as proximity ligation-free, robust, sensitive technique profile genome-wide at high-resolution among elements. detects looping accessible regions single...
The contribution of three-dimensional genome organization to physiological ageing is not well known. Here we show that large-scale chromatin reorganization distinguishes young and old bone marrow progenitor (pro-) B cells. These changes result in increased interactions at the compartment level reduced within topologically associated domains (TADs). gene encoding Ebf1, a key cell regulator, switches from A with age. Genetically reducing Ebf1 recapitulates some features pro-B TADs are most age...
A few families of transposable elements (TEs) have been shown to evolve into cis -regulatory (CREs). Here, extend these studies all classes TEs in the human genome, we identified widespread enhancer-like repeats (ELRs) and find that ELRs reliably mark cell identities, are enriched for lineage-specific master transcription factor binding sites, mostly primate-specific. In particular, MIR L2 TE whose abundance co-evolved across chordate genomes, found as most types examined. frequently share...
Mounting evidence has shown that ambient PM2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM2.5. In this study, 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore adipogenic potential After 8 days exposure, adipocyte fatty acid uptake lipid accumulation were significantly increased, cells promoted in a concentration-dependent manner. Transcriptome lipidome analyses revealed...
Although chronic inflammation increases many cancers' risk, how facilitates cancer development is still not well studied. Recognizing whether and when inflamed tissues transition to cancerous of utmost importance. To unbiasedly infer molecular events, immune cell types, secreted factors contributing the inflammation-to-cancer (I2C) transition, we develop a computational package called "SwitchDetector" based on liver, gastric, colon I2C data. Using it, identify angiogenesis associated with...
Distant metastases occur when non-small cell lung cancer (NSCLC) is at late stages. Bone metastasis one of the most frequent NSCLC and leads to poor prognosis. It has been reported that high expression BMP2 in correlates with survival, but whether contributes bone remains largely unknown. The activation BMP signalling found metastatic tumours mice Lewis carcinoma predicts survival human NSCLC. can enhance carcinoma. Moreover, secreted by stroma fibroblasts promote migration invasion cells....
Investigating chromatin interactions between regulatory regions such as enhancer and promoter elements is vital for understanding the regulation of gene expression. Compared to Hi-C its variants, emerging 3D mapping technologies focusing on enriched signals, TrAC-looping, reduce sequencing cost provide higher interaction resolution cis-regulatory elements. A robust pipeline needed comprehensive interpretation these data, especially loop-centric analysis. Therefore, we have developed a new...
Recently, multiple single-cell assays were developed for detecting histone marks at the level. These techniques are either limited by low cell throughput or sparse reads which limit their applications. To address these problems, we introduce indexing immunocleavage sequencing (iscChIC-seq), a multiplex method based on TdT terminal transferase and T4 DNA ligase-mediated barcoding strategy ChIC-seq, is capable of readily analyzing modifications across tens thousands single cells in one...
Differentiation of human embryonic stem cells into mesendoderm (ME) is directed by extrinsic signals and intrinsic epigenetic modifications. However, the dynamics these modifications mechanisms which regulate during initiation ME differentiation remain elusive. In this study, we report that levels histone H3 Lys-27 trimethylation (H3K27me3) decrease initiation, essential for subsequent induced combined effects activin Wnt signaling. Furthermore, demonstrate mediates H3K27me3 via...
Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability real human conditions. Here, we developed an silico screen vivo using a reference single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) 8,476 genes generated from the TCGA database. We core-signature drug-to-gene (csD2G) software scan 3,546 treatment profiles against signatures. csD2G significantly outperformed conventional cell...
The spatial folding of eukaryotic genome plays a key role in function. We report here that our recently developed method, Hi-TrAC, which specializes detecting chromatin loops among accessible genomic regions, can detect active sub-TADs with median size 100 kb, most harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These are characterized by highly enriched histone mark H3K4me1 chromatin-binding...
Different mechanisms govern the first and second steps of IgH gene recombination.