Biology subjects

Liu, Q.

Publications and source records attributed to Liu, Q..

At least 217 records · Page 12Linked to original sources

bioRxiv2025

Identification of a neural basis for energy expenditure in the arcuate hypothalamus

Given the evolutionary instinct for caloric intake and the tendency for weight rebound after discontinuing dietary interventions or medications, increasing energy expenditure emerges as an alternative obesity treatment. However, neural regulation of energy expenditure remains poorly understood. Here, we report that a hypothalamic neuronal subtype, characterized by Crabp1 expression, establishes connections with multiple hypothalamic nuclei to regulate energy expenditure in mice. Inactivation of Crabp1 neurons reduces physical activity, body temperature, and adaptive thermogenesis, leading to an obese phenotype. Conversely, activation of these neurons increases energy expenditure and mitigates diet-induced obesity. Structural and functional analyses reveal that Crabp1 neurons promote energy metabolism through a "one-to-many" projection pattern. While Crabp1 neurons are rapidly activated by cold exposure and physical activity, prolonged light exposure abrogates their firing and may mediate light-induced metabolic disorder. Together, we reveal a neural basis that integrate various physiological and environmental stimuli to control energy expenditure and body weight.

neuroscience↗

bioRxiv2025

Coordinated changes in thymic stromal and hematopoietic cells that define the perinatal to juvenile transition

T cells in the perinatal thymus have distinct phenotypes and functions that may be instructed by age-specific features of the microenvironment. We evaluated molecular and cellular profiles of thymic stromal cells, including thymic epithelial cells (TECs), mesenchyme, endothelium, and hematopoietic antigen presenting cells (hAPCs), from birth through one-month of age in mice. Single-cell transcriptional profiling, flow cytometry, and immunohistochemistry revealed coordinated stromal changes accompanied by altered thymocyte differentiation at defined transitional ages during the shift from perinatal growth to juvenile homeostasis, which was mirrored in humans. These analyses link diminished IGF2 expression by mesenchymal cells with activation of the RB pathway in TECs at the transition. Moreover, a coordinated increase in type I interferon signaling in stroma across the transition is associated with altered antigen processing and presentation signatures in TECs and hAPCs. Collectively, these datasets provide a resource to interrogate thymic stroma across the perinatal to juvenile transition.

immunology↗

bioRxiv2025

Maintenance DNA methylation is required for induced regulatory T cell reparative function following viral pneumonia

FOXP3+ natural regulatory T cells (nTregs) promote resolution of inflammation and repair of epithelial damage following viral pneumonia-induced lung injury, thus representing a cellular therapy for patients with acute respiratory distress syndrome (ARDS). Whether in vitro induced Tregs (iTregs), which can be rapidly generated in substantial numbers from conventional T cells, also promote lung recovery is unknown. nTregs require specific DNA methylation patterns maintained by the epigenetic regulator, ubiquitin-like with PHD and RING finger domains 1 (UHRF1). Here, we tested whether iTregs promote recovery following viral pneumonia and whether iTregs require UHRF1 for their pro-recovery function. We found that adoptive transfer of iTregs to mice with influenza virus pneumonia promotes lung recovery and that loss of UHRF1-mediated maintenance DNA methylation in iTregs leads to reduced engraftment and a delayed repair response. Transcriptional and DNA methylation profiling of adoptively transferred UHRF1-deficient iTregs that had trafficked to influenza-injured lungs demonstrated transcriptional instability with gain of effector T cell lineage-defining transcription factors. Strategies to promote the stability of iTregs could be leveraged to further augment their pro-recovery function during viral pneumonia and other causes of ARDS.

immunology↗

bioRxiv2025

Multi-modal Diffusion Model with Dual-Cross-Attention for Multi-Omics Data Generation and Translation

Single-cell multi-omics technologies offer unprecedented opportunities to decipher complex cellular mechanisms. To overcome experimental limitations in scale, cost, and coverage, powerful computational methods are essential for integrating diverse data modalities and generating high-fidelity in-silico data. In this paper, we present scDiffusion-X, a latent diffusion model specifically designed for this purpose. The core innovation is a Dual-Cross-Attention (DCA) module that adaptively learns intricate, hidden relationships between different molecular modalities, offering a more flexible and interpretable approach than traditional integration strategies. Extensive benchmarking experiments demonstrate that scDiffusion-X excels at generating realistic multi-omics data, preserving cellular heterogeneity and global data structures with excellent scalability. Distinct from existing multi-omics simulators, scDiffusion-X uniquely enables high-fidelity modality translation by predicting one molecular modality from another and provides robust uncertainty quantification. Beyond data generation, we designed a gradient-based interpretation framework to transform DCA module into a discovery tool, enabling inference of comprehensive cell-type-specific heterogeneous gene regulatory networks (GRNs). By integrating state-of-the-art generative modeling with deep biological interpretability, scDiffusion-X serves as a powerful tool for dissecting regulatory relationships, predicting perturbation responses, poised to accelerate discovery in single-cell multi-omics research.

bioinformatics↗

bioRxiv2025

Virus-host interactome reveals host cellular pathways perturbed by tick-borne encephalitis virus infection

Tick-borne encephalitis virus (TBEV) poses an increasingly significant threat to public health. Here, we delved into the virus-host interactome and discovered that TBEV has a profound impact on multiple host cellular pathways. Viral pre-membrane protein (prM), non-structural proteins NS1, NS2B3, NS4A, and NS5 remodel the hosts innate immune responses. PrM and NS2B3 are involved in autophagy, NS4A is associated with neurodegenerative diseases, and NS5 participates in spliceosome dynamics, ribosomal biogenesis, cell cycle regulation, and DNA damage response. Notably, TBEV infection causes G0/G1 cell cycle arrest in host cells. NS5 interacts with histone acetyltransferase P300 to upregulate P16 expression, suppressing CDK4 and resulting in cell cycle arrest. Elevated P16 and reduced CDK4 levels were observed in TBEV-infected brain organoids. The P300 inhibitors and CDK4 agonist can reverse virus-induced cell cycle arrest and inhibit viral replication. Further analysis uncovered potential antiviral targets like KAT6A, XIAP, and RIOK1/BRD9. These findings provide valuable insights into TBEV pathogenicity and hold promise for antiviral drug development.

microbiology↗

bioRxiv2025

Myelin transcription factors 1 and 3 have overlapping but distinct roles in insulin secretion and survival of human β cells

Aims/hypothesisGenetic and environmental factors work together to cause islet beta-cell failure, leading to type 2 diabetes (T2D). How these factors are integrated to regulate beta cells remains largely unclear. Based on our previous findings that the family of Myelin transcription factors (MYT1, MYT1L, and ST18) prevents mouse beta-cell failure by repressing the overactivation of stress response, their regulation by obesity-related nutrition signals in human beta cells, and their association with T2D, we postulate that these factors prevent human beta-cell failure under normal physiology and obesity-related stress. MethodsMYT1 or ST18 were knocked down in primary human beta cells using shRNA. Beta-cell survival, secretory function, and gene expression were examined after islet cells were cultured in vitro or xenotransplanted into mice under normal or obesity-related stress. ResultsIn culture, MYT1-knockdown (KD) caused beta-cell death, while ST18-KD compromised glucose-stimulated insulin secretion. Under obesity-induced stress as xenotransplants, ST18-KD also caused beta-cell death. Accordingly, MYT1-KD deregulated several genes and genesets in cell death and cellular stress response, while ST18-KD deregulated those regulating stress response, mitochondria, and ion channels. Corresponding to these gene expression changes, ST18-KD reduces glucose-stimulated Ca2+ influx in beta cells. In addition, the MYT1- and ST18-regulated genes are enriched for T2D-associated loci, with an enrichment of 2.05-fold relative to random distribution. Conclusions/interpretationThe MYT TFs complement each other to integrate genetic and environmental factors to prevent beta-cell failure and T2D, with their major effects exerted on beta-cell viability and/or Ca2+ influx. Graphical AbstractNutrient-responsive transcription factors MYT1 and ST18 regulate human beta-cell survival and secretory functions. Under low metabolic stress, MYT1 regulates cell survival while ST18 regulates insulin secretion. Under high metabolic stress, ST18 also regulates beta-cell survival. MYT1, at least partly, regulates cell survival through stress-related apoptotic processes, while ST18 regulates insulin secretion via Ca2+ influx. Research in context summaryO_ST_ABSBackgroundC_ST_ABSO_LIThe myelin transcription factors (MYT TFs, including MYT1, MYT1l, and ST18) prevent mouse beta-cell failure by depressing the overactivation of stress-response genes. C_LIO_LISNPs in all three MYT loci are associated with human type 2 diabetes. C_LIO_LIThe expression and nuclear localization of MYT1 and ST18 were increased in primary human beta cells under acute metabolic stress but downregulated in type 2 diabetes. C_LIO_LIThe co-knockdown of MYT1, MYT1L, and ST18 in a human beta-cell line resulted in apoptosis. C_LI Key questionO_LIHow does MYT1 or ST18 regulate human beta-cell function and survival? C_LI New findingsO_LIMYT1 prevents human beta-cell death under normal and metabolic stress conditions, corresponding to deregulation of a few genes involved in cell death under cellular stress. C_LIO_LIST18 promotes insulin secretion under normal physiological conditions by regulating Ca2+ influx and prevents beta-cell death under metabolic stress. C_LIO_LIThe MYT1- and ST18-regulated genes are enriched for type 2 diabetes-risk loci. C_LI Clinical impactO_LIRegulators of the MYT-TF activities could be explored to delay/prevent beta-cell failure and the development of type 2 diabetes. C_LI

cell biology↗

bioRxiv2025

Pooled screening identifies combinatorial CAR signaling domains for next-generation CAR-M immunotherapies

Chimeric antigen receptor-engineered macrophages (CAR-Ms) hold great promise for solid tumor immunotherapy. The intracellular domains (ICDs) of CARs determine the phenotypic output of therapeutic macrophages but remain largely unexplored. Here, we constructed a CAR library containing 131 unique signaling domains derived from native immune receptors and identified 17 ICDs that enhance macrophage phagocytosis, inflammatory responses, or tumor infiltration in vitro and in vivo. We further developed a scalable 3 barcode technology, CARode, to uniquely label and trace ICD variants within large-scale combinatorial CAR library and applied it to single-cell RNA sequencing and single-cell CAR analysis to assess the synergetic effects of ICD combinations on macrophage activation. Our approach uncovered a novel CD40-LY9-FCRL1 chimeric receptor that modulates the tumor microenvironment and improves solid tumor clearance. In conclusion, our findings demonstrate that pooled screening can accelerate the discovery of complex ICD constructs, providing a powerful platform for engineering macrophage-based immunotherapies.

bioengineering↗

bioRxiv2025

MethylProphet: A Generalized Gene-Contextual Model for Inferring Whole-Genome DNA Methylation Landscape

AO_SCPLOWBSTRACTC_SCPLOWDNA methylation (DNAm) is a key epigenetic modification that regulates gene expression and is pivotal in development and disease. However, profiling DNAm at genome scale is challenging: of [~]28 million CpG sites in the human genome, only about 1-3% are typically assayed in common datasets due to technological limitations and cost. Recent deep learning approaches, including masking-based generative Transformer models, have shown promise in capturing DNAm-gene expression relationships, but they rely on partially observed DNAm values for unmeasured CpGs and cannot be applied to completely unmeasured samples. To overcome this barrier, we introduce MethylProphet, a gene-guided, context-aware Transformer model for whole-genome DNAm inference without any measured DNAm input. MethylProphet compresses comprehensive gene expression profiles ([~]25K genes) through an efficient bottleneck multilayer perceptron, and encodes local CpG sequence context with a specialized DNA tokenizer. These representations are integrated by a Transformer encoder to predict site-specific methylation levels. Trained on large-scale pan-tissue whole-genome bisulfite sequencing data from ENCODE (1.6 billion CpG-sample pairs, [~]322 billion tokens), MethylProphet demonstrates strong performance in hold-out evaluations, accurately inferring DNAm at unmeasured CpGs and generalizing to unseen samples. Furthermore, application to TCGA pan-cancer data (chromosome 1, 9,194 samples; [~]450 million training pairs, 91 billion tokens) highlights its potential for pan-cancer whole-genome methylome imputation. MethylProphet offers a powerful and scalable foundation model for epigenetics, providing high-resolution methylation landscape reconstruction and advancing both biological research and precision medicine.

bioinformatics↗

bioRxiv2025

Solubilization of Membrane Proteins using designed protein WRAPS

The development of therapies and vaccines targeting integral membrane proteins has been complicated by their extensive hydrophobic surfaces, which can make production and structural characterization difficult. Here we describe a general deep learning-based design approach for solubilizing native membrane proteins while preserving their sequence, fold, and function using genetically encoded de novo protein WRAPs (Water-soluble RFdiffused Amphipathic Proteins) that surround the lipid-interacting hydrophobic surfaces, rendering them stable and water-soluble without the need for detergents. We design WRAPs for both beta-barrel outer membrane and helical multi-pass transmembrane proteins, and show that the solubilized proteins retain the binding and enzymatic functions of the native targets with enhanced stability. Syphilis vaccine development has been hindered by difficulties in characterizing and producing the outer membrane protein antigens; we generated soluble versions of four Treponema pallidum outer membrane beta barrels which are potential syphilis vaccine antigens. A 4.0 [A] cryo-EM map of WRAPed TP0698 is closely consistent with the design model. WRAPs should be broadly useful for facilitating biochemical and structural characterization of integral membrane proteins, enabling therapeutic discovery by screening against purified soluble targets, and generating antigenically intact immunogens for vaccine development.

biochemistry↗

bioRxiv2025

Nipah virus matrix protein utilizes cortical actin to stabilize the virus assembly sites and promote budding

Several families of enveloped viruses assemble and bud from the host cell plasma membranes (PM), including paramyxoviruses. Nipah virus (NiV) is a deadly zoonotic paramyxovirus causing yearly outbreaks in Southeast Asia with >75% mortality. NiV encodes matrix proteins (M) that drive assembly and budding. NiV-M forms dimers and interacts with membrane lipids in the host cells PM for budding. Using single-molecule localization microscopy and single-particle tracking, we show that the host F-actin maintains the nanoscale organization of NiV assembly sites at the PM. This F-actin-dependent integrity of NiV assembly sites is observed at the membrane retention stage after the assembly process is complete, rather than during the recruitment of NiV-M molecules to these sites. NiV-M interacts with actin via its C-terminal domain. We also show that the actin-branching factor, Arp2/3 complex, promotes virus-like-particle production. Meanwhile, inhibiting Arp2/3 disfavors the PM retention of NiV assembly sites and NiV-M-mediated generation of membrane protrusions, but does not affect the assembly rate. This suggests that Arp2/3-nucleated actin polymerization and branching are critical for maintaining NiV-M assembly sites at the PM, allowing it to facilitate membrane protrusion generation for virus budding. Our findings support the following model: NiV-M interacts with F-actin through its C-terminus to remain at the host PM after assembly completion. This F-actin-dependent retention is promoted by the Arp2/3-driven actin branching and polymerization, which also drives the formation of NiV-M-induced membrane protrusions necessary for virus budding. SignificanceNipah virus (NiV) is a deadly paramyxovirus capable of animal-animal and animal-human transmissions. To produce a NiV particle, the NiV matrix protein (M) must create an assembly site by binding to the surface of an infected cell and pushing the cell membrane outward for virus budding. To do so, the NiV matrix protein must co-opt or overcome an actin network underneath the cell membrane. We provide single-molecule evidence that M interacts with the actin cytoskeleton for membrane retention but not recruitment of M to existing assembly sites. This process is promoted by the Arp2/3-driven actin branching and polymerization. Our findings suggest the role of actin remodeling in NiV budding and identify a druggable site at the C-terminus of NiV-M.

microbiology↗

bioRxiv2025

Follicular mural granulosa cells stockpile glycogen to fuel corpus luteum pre-vascularization

The corpus luteum (CL) arises from the luteinization of follicular granulosa cells (GCs) and theca cells, marked by rapid progesterone elevation and angiogenesis. Intriguingly, angiogenesis lags behind progesterone elevation, creating an avascular phase during which luteal cells must fuel intensive steroidogenesis without perfusion. How the avascular CL meets this energetic demand remains a mystery. Here, we reveal a novel cellular adaptive mechanism-GC energy storage (GCES)-that resolves this enigma. We demonstrate that upon luteinization initiation, GCs enter a metabolically quiescent state yet enhance glucose uptake via SLC2A1, converting the glucose into glycogen through the hCG (LH)-MAPK-RUNX1-Insulin signaling axis. Catabolism of this glycogen reserve supplies the energy required for the avascular CL, ensuring normal luteogenesis. GCES is evolutionarily conserved across species. Genetic or pharmacological disruption of GCES or glycogenolysis induces luteal insufficiency, whereas timely glucose administration enhances GCES, improving luteal function and optimize reproductive outcome in both mouse and ovine models. In human study, orally intake of glucose post-hCG significantly augments GCES and enhances progesterone production in women. These results advance luteal physiology by uncovering a universal reproductive principle with direct clinical implications.

developmental biology↗

bioRxiv2025

The membrane topology problem inherent in ciliogenesis is solved by ciliary recruitment of a phospholipid flippase

The cilium is a slender cellular projection whose membrane transduces signals essential in development and homeostasis. Although assembly of the axonemal core of the organelle is well-studied, the mechanisms that underlie formation of the [~]250 nm diameter ciliary membrane from oppositely curved 50-100 nm diameter pre-ciliary vesicles remain poorly understood. Here we report that during ciliogenesis in the bi-ciliated alga, Chlamydomonas reinhardtii, aminophospholipid flippase 2 (ALA2) is recruited laterally from a reservoir on the plasma membrane onto the nascent ciliary membrane where it transfers conically shaped phosphatidyl ethanolamine (PE) from the outer to the inner leaflet. In cells lacking ALA2, initiation of cilia regeneration after experimentally induced de-ciliation is delayed, PE flipping is impaired, the ciliary membrane becomes distorted, and cilia that do form are shorter than wild type. Our results uncover a membrane topology problem inherent in ciliogenesis and demonstrate that it is resolved by a phospholipid flippase. HighlightsO_LIMembranes of pre-ciliary vesicles reverse curvature to become the ciliary membrane C_LIO_LIUpon initiation of ciliogenesis, plasma membrane ALA2 transits laterally to cilia C_LIO_LIThe ciliary membranes of ala2 mutants fail to conform to axonemal shape C_LIO_LIALA2 flips PE to establish ciliary membrane curvature C_LI

cell biology↗

bioRxiv2025

Distinct Control of histone H1 expression within the Histone Locus body by CRAMP1

Proper histone gene expression is critical to cell viability and maintaining genomic integrity. Multiple histone genes organized into three genomic loci encode for replication coupled core and linker histones. Histone gene expression and transcript processing is orchestrated in the histone locus body (HLB) within the nucleus. We identified human CRAMP1 as a selective regulator of linker histone H1 expression. CRAMP1 is recruited to the HLB in RPE1hTERT cells. Affinity purification shows that CRAMP1 physically associates the HLB component GON4L (a.k.a. YARP). We show that the PAH domains of GON4L interact with CRAMP1. CRAMP1 disruption results in a loss of histone H1 expression and a reduction in H1 protein. CRAMP1 occupies the unmethylated promoters of the replication coupled linker histone genes that reside within the histone locus body, and the replication independent histone H1 loci, which reside in a region of the genome without other histone genes. Together these data identify CRAMP1 as a novel and selective regulator of histone H1 gene expression.

genomics↗

bioRxiv2025

Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohns disease (CD) model (Tnf{Delta}ARE/+), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the hosts immune susceptibility to drive region-specific disease. We identified Chlamydia muridarum, an intracellular bacterium and murine counterpart to the human sexually transmitted C. trachomatis, as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD. Disease manifestation in the AC depends on indoleamine 2,3-dioxygenase (IDO1) activity induced by hypersensitive surface secretory cells in genetically susceptible hosts. Single-cell and microbial analyses of human specimens also implicates this pathobiont-epithelial IDO1 pathway in patients with a history of CD in the AC. Our findings demonstrate that genetic and microbial factors can independently drive region-specific disease and provide a unique model to study CD specific to the AC.

cell biology↗

bioRxiv2024

GP-ML-DC: An Ensemble Machine Learning-Based Genomic Prediction Approach with Automated Two-Phase Dimensionality Reduction via Divide-and-Conquer Techniques

Traditional machine learning (ML) and deep learning (DL) methods for genome prediction often face challenges due to the imbalance between the limited number of samples (n) and the large number of single nucleotide polymorphisms (SNPs) (p), where n is much smaller than p. To address this, we propose GP-ML-DC, an innovative genome predictor that combines traditional ML and DL models with a unique two-phase, parameter-free dimensionality reduction technique. Initially, GP-ML-DC reduces feature dimensionality by characterizing genes as features. Building on big data methodologies, it employs a divide-and-conquer approach to segment gene regions into multiple haplotypes, further decreasing dimensionality. Each haplotype segment is processed by a sub-task based on traditional ML, followed by integration via a neural network that synthesizes the results of all sub-tasks. Our experiments, conducted on four cattle milk-related traits using ten-fold cross-validation and independent testing, show that GP-ML-DC significantly surpasses current state-of-the-art genome predictors in prediction performance.

bioinformatics↗

bioRxiv2024

Effects of combined application of organic fertilizer and inorganic fertilizer on soil and yield of Gaodan grass

Using Sorghum bicolor x sudanense as test material, the effects of inorganic fertilizer and different proportions of organic fertilizer application on soil properties, yield and quality of sorghum were studied under conventional nitrogen application levels, aiming to provide data support for efficient production of green cycle forage. Five treatments were set up in the experiment, namely blank treatment (CK), conventional fertilization (HF), equivalent cow manure organic fertilizer (NF2), equivalent sheep manure organic fertilizer (YF2), 150% equivalent cow manure organic fertilizer (NF5) and 150% equivalent sheep manure organic fertilizer (YF5). In general, NF5 treatment was excellent in improving soil organic matter, enzyme activity and nutrient content, and the yield of Gaodan grass was significantly increased.

plant biology↗

bioRxiv2024

Causal disentanglement for single-cell representations and controllable counterfactual generation

Conducting disentanglement learning on single-cell omics data offers a promising alternative to traditional black-box representation learning by separating the semantic concepts embedded in a biological process. We present CausCell, which incorporates the causal relationships among disentangled concepts within a diffusion model to perform disentanglement learning, with the aim of increasing the explainability, generalizability and controllability of single-cell data, including spatial and temporal omics data, relative to those of the existing black-box representation learning models. Two quantitative evaluation scenarios, i.e., disentanglement and reconstruction, are presented to conduct the first comprehensive single-cell disentanglement learning benchmark, which demonstrates that CausCell outperforms the state-of-the-art methods in both scenarios. Additionally, CausCell can implement controllable generation by intervening with the concepts of single-cell data when given a causal structure. It also has the potential to uncover biological insights by generating counterfactuals from small and noisy single-cell datasets.

bioinformatics↗

bioRxiv2024

Chemical perturbations impacting histone acetylation governcolorectal cancer differentiation

Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype. Unbiased profiling of histone posttranslational modifications induced by HDAC1/2 inhibition nominated acetylation of specific histone lysine residues as potential regulators of differentiation. Genome-wide assessment of implicated marks indicated that H3K27ac gains at HDAC1/2-bound regions associated with open chromatin and upregulation of differentiation genes upon HDAC1/2 inhibition. Disrupting H3K27ac by degrading acetyltransferase EP300 rescued HDAC1/2 inhibitor-mediated differentiation of a patient-derived CRC model using single cell RNA-sequencing. Genetic screens revealed that DAPK3 contributes to CRC differentiation induced by HDAC1/2 inhibition. These results highlight the importance of specific chemically targetable histone modifications in governing cancer cell states and epigenetic reprogramming as a therapeutic strategy in CRC. BRIEF SUMMARYHDAC1/2 inhibition promotes colorectal cancer differentiation via gains in H3K27ac, which can be reversed by blocking its acetyltransferase EP300.

cancer biology↗