The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells.

Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX. We found that JunB regulated iNKT cell development and that the expression of genes that were targets of both JunB and the iNKT cell master transcription factor PLZF was UTX dependent. We identified iNKT cell super-enhancers and demonstrated that UTX-mediated regulation of super-enhancer accessibility was a key mechanism for commitment to the iNKT cell lineage. Our findings reveal how UTX regulates the development of iNKT cells through multiple epigenetic mechanisms.

Epigenome-augmented eQTL-hotspots reveal genome-wide transcriptional programs in 36 human tissues.

Expression quantitative trait loci (eQTLs) are used to inform the mechanisms of transcriptional regulation in eukaryotic cells. However, the specificity of genome-wide eQTL identification is limited by stringent control for false discoveries. Here, we described a method based on the non-homogeneous Poisson process to identify 125 489 regions with highly frequent, multiple eQTL associations, or 'eQTL-hotspots', from the public database of 59 human tissues or cell types. We stratified the eQTL-hotspots into two classes with their distinct sequence and epigenomic characteristics. Based on these classifications, we developed a machine-learning model, E-SpotFinder, for augmented discovery of tissue- or cell-type-specific eQTL-hotspots. We applied this model to 36 tissues or cell types. Using augmented eQTL-hotspots, we recovered 655 402 eSNPs and reconstructed a comprehensive regulatory network of 2 725 380 cis-interactions among eQTL-hotspots. We further identified 52 012 modules representing transcriptional programs with unique functional backgrounds. In summary, our study provided a framework of epigenome-augmented eQTL analysis and thereby constructed comprehensive genome-wide networks of cis-regulations across diverse human tissues or cell types.

Complexity of enhancer networks predicts cell identity and disease genes revealed by single-cell multi-omics analysis.

Many enhancers exist as clusters in the genome and control cell identity and disease genes; however, the underlying mechanism remains largely unknown. Here, we introduce an algorithm, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. The complexity of enhancer networks is assessed by two metrics: the number of enhancers and the frequency of predicted enhancer interactions (PEIs) based on chromatin co-accessibility. We apply eNet algorithm to a human blood dataset and find cell identity and disease genes tend to be regulated by complex enhancer networks. The network hub enhancers (enhancers with frequent PEIs) are the most functionally important. Compared with super-enhancers, enhancer networks show better performance in predicting cell identity and disease genes. eNet is robust and widely applicable in various human or mouse tissues datasets. Thus, we propose a model of enhancer networks containing three modes: Simple, Multiple and Complex, which are distinguished by their complexity in regulating gene expression. Taken together, our work provides an unsupervised approach to simultaneously identify key cell identity and disease genes and explore the underlying regulatory relationships among enhancers in single cells.

Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high-resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed scRankXMBD, a computational framework to prioritize prognostic-associated cell subpopulations based on within-cell relative expression orderings of gene pairs from single-cell transcriptomes. scRankXMBD achieves higher precision and concordance compared with five existing methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Our work facilitates the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology. scRankXMBD is available at https://github.com/xmuyulab/scRank-XMBD. (XMBD:Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.).

Enhancer selectivity across cell types delineates three functionally distinct enhancer-promoter regulation patterns.

BACKGROUND: Multiple enhancers co-regulating the same gene is prevalent and plays a crucial role during development and disease. However, how multiple enhancers coordinate the same gene expression across various cell types remains largely unexplored at genome scale. RESULTS: We develop a computational approach that enables the quantitative assessment of enhancer specificity and selectivity across diverse cell types, leveraging enhancer-promoter (E-P) interactions data. We observe two well-known gene regulation patterns controlled by enhancer clusters, which regulate the same gene either in a limited number of cell types (Specific pattern, Spe) or in the majority of cell types (Conserved pattern, Con), both of which are enriched for super-enhancers (SEs). We identify a previously overlooked pattern (Variable pattern, Var) that multiple enhancers link to the same gene, but rarely coexist in the same cell type. These three patterns control the genes associating with distinct biological function and exhibit unique epigenetic features. Specifically, we discover a subset of Var patterns contains Shared enhancers with stable enhancer-promoter interactions in the majority of cell types, which might contribute to maintaining gene expression by recruiting abundant CTCF. CONCLUSIONS: Together, our findings reveal three distinct E-P regulation patterns across different cell types, providing insights into deciphering the complexity of gene transcriptional regulation.

An Unexpected Finding of Klinefelter Syndrome during Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) Genetic Analysis.

BACKGROUND: Klinefelter syndrome is a common sex chromosome abnormality in males, characterized by an extra X chromosome compared to normal males. Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked incomplete dominant defect disorder. In this study, we reported the unexpected detection of Klinefelter syndrome in a patient with G6PD. METHODS: G6PD enzyme activity was measured by immunoenzyme assay, and genetic analysis was performed using a fluorescent PCR melting curve method (PCR-melting curve). Sex chromosome number abnormalities were detected by multiplex ligation-dependent probe amplification (MLPA). The patient also underwent peripheral blood chromosome karyotype analysis. RESULTS: The patient's G6PD and 6PGD enzyme activities were 21.34 U/L and 22.85 U/L, respectively, and their ratio was below the reference range (0.93). The PCR-melting curve displayed a c.1388 heterozygous mutation in this boy, and the Sanger sequencing provided the same results. MLPA results suggested the presence of approxi-mately two copies of the X-chromosome in the boy. Finally, chromosome karyotype analysis confirmed that the boy had Klinefelter syndrome with a karyotype of 47, XXY. CONCLUSIONS: Klinefelter syndrome was accidentally detected during G6PD genetic analysis in a male. X-chromosomes can interfere with the results of G6PD genetic analysis and should be noted.

Hb Guigang [α90 (FG2)Lys→Asn; HBA1:c.273G˃T]: a Novel α-Globin Chain Variant.

BACKGROUND: New hemoglobin (Hb) variants are constantly being updated as assays are developed and the testing population expands. Here, we report a novel Hb variant, named Hb Guigang. METHODS: Hemoglobin (Hb) analysis was analyzed by capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Glycated hemoglobin was performed by CE and HPLC. Routine genetic analysis was done with Gap-PCR and PCR-reverse dot-blot hybridization. The hemoglobin variant was identified by Sanger sequencing. RESULTS: CE of three cases showed the presence of Hb variants in Zone 5 and Zone 12, respectively. HPLC indicated an elevated P3 peak, suggesting the possible presence of the Hb variant. Hb A1c was measured by CE and HPLC, and the results were 6.7% and 4.76%, respectively. Sanger sequencing confirmed an AAG˃AAT mutation at codon 90 of the HBA1 gene. This mutation was reported for the first time, and we named it Hb Guigang based on the proband's place of residence. CONCLUSIONS: Hb Guigang with normal hematological parameters was separated and quantified by CE, whereas HPLC suggested that Hb Guigang co-eluted with the P3 peaks and could not be quantified.

Diagnostic Value of Ultrasound Endoscopy-Guided Fine-Needle Aspiration for Peritoneal Lesions.

Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.

Asymptotic analysis on a new stochastic epidemic model involving isolation mechanism.

In this paper, a new stochastic epidemic model is established and the dynamical behavior of its solutions is studied for this model. A deterministic epidemic model (ordinary differential equation) is first proposed by considering the isolation mechanism, and the transmission probability function is determined by a Wells-Riley model method to analyze the transmission in the quarantine. For this deterministic model, the basic reproduction number R0 is computed and it is used to determine the existence of disease-free and positive equilibria. The linearized stability of the equilibria is also discussed by analyzing the distribution of eigenvalues of the linear system. Following that, a corresponding stochastic epidemic model is further established by introducing stochastic disturbance. Then, the extinction result of the model is derived also with the help of the basic reproduction number R0s. Furthermore, by applying the theory of Markov semigroups, it is proved that the densities of the distributions of the solutions can converge to an invariant density or sweeping under certain conditions. At last, some numerical simulations are provided and discussed to illustrate the practicability of the model and the obtained theoretical results.

Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions.

Polycomb repressive complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during blood cell development. An erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers. We further examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 subcomplex lacking EED. EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1 to EZH2 targets. Thus, the lineage- and developmental stage-specific regulation of PRC2 subunit composition leads to a switch from canonical silencing to non-canonical functions during blood stem cell specification.

Hericium erinaceus polysaccharide improves the microstructure, immune function, proliferation and reduces apoptosis of thymus and spleen tissue cells of immunosuppressed mice.

In order to study the effect of Hericium erinaceus polysaccharide (HEP) on the immune and antioxidation functions of immunosuppressed mice. The control group received distilled water orally and the model and experimental groups I, II, and III received 0, 80, 160, and 320 mg/kg HEP respectively for a fortnight after re-molding with cyoclphosphnalide (CTX). Compared with the control group, the secretion of IL-2, IL-4, and IFN-γ, the activity or content of T-AOC, T-SOD, and GSH-PX, and the expression of PCNA mRNA in the thymus and spleen were reduced in immunosuppressed mice (P < .05 or P < .01). Compared with immunosuppressed mice, the levels of IL-2, IFN-γ, and GSH-PX and the PCNA mRNA expression of spleen and thymus were increased (P < .05 or P < .01), and the microstructure were also obviously improved in the experimental group III. Overall, 320 mg/kg of HEP significantly improved the immune and antioxidant functions.

Enhancer dependence of cell-type-specific gene expression increases with developmental age.

How overall principles of cell-type-specific gene regulation (the "logic") may change during ontogeny is largely unexplored. We compared transcriptomic, epigenomic, and three-dimensional (3D) genomic profiles in embryonic (EryP) and adult (EryD) erythroblasts. Despite reduced chromatin accessibility compared to EryP, distal chromatin of EryD is enriched in H3K27ac, Gata1, and Myb occupancy. EryP-/EryD-shared enhancers are highly correlated with red blood cell identity genes, whereas cell-type-specific regulation employs different cis elements in EryP and EryD cells. In contrast to EryP-specific genes, which exhibit promoter-centric regulation through Gata1, EryD-specific genes rely more on distal enhancers for regulation involving Myb-mediated enhancer activation. Gata1 HiChIP demonstrated an overall increased enhancer-promoter interactions at EryD-specific genes, whereas genome editing in selected loci confirmed distal enhancers are required for gene expression in EryD but not in EryP. Applying a metric for enhancer dependence of transcription, we observed a progressive reliance on cell-specific enhancers with increasing ontogenetic age among diverse tissues of mouse and human origin. Our findings highlight fundamental and conserved differences at distinct developmental stages, characterized by simpler promoter-centric regulation of cell-type-specific genes in embryonic cells and increased combinatorial enhancer-driven control in adult cells.

Insights into multisource sludge distributed in the Yangtze River basin, China: Characteristics, correlation, treatment and disposal.

Sludge is the by-product of wastewater treatment process. Multisource sludge can be defined as sludge from different sources. Based on the sludge properties of five typical cities in the Yangtze River basin, including Jiujiang, Wuhu, Lu'an, Zhenjiang and Wuhan, this study investigated and summarized the characteristic variations and distribution differences of multiple indicators and substances from municipal sludge, dredged sludge, and river and lake sediments. The results demonstrated pH of multisource sludge was relatively stable in the neutral range. Organic matter and water content among municipal sludge were high and varied considerably between different wastewater treatment plants. Dredged sludge had an obviously higher sand content and wider particle distribution, which could be considered for graded utilization depending on its size. The nutrients composition of river and lake sediments was usually stable and special, with lower nitrogen and phosphorus content but higher potassium levels. The sources of heavy metals and persistent organic pollutants in multisource sludge were correlated, generally much higher among municipal sludge than dredged sludge and river and lake sediments, which were the most important limitation for final land utilization. Despite various properties of multisource sludge, the final fate and destination have some overall similarities, which need to be supplemented and improved by standards and laws. The study provided a preliminary analysis of suitable technical routes for municipal sludge, dredged sludge, river and lake sediments based on their different characteristics respectively, which was of great significance for multisource sludge co-treatment and disposal in the future of China.

Large-Grain Spanning Monolayer Cu2 ZnSnSe4 Thin-Film Solar Cells Grown from Metal Precursor.

The persistent double layer structure whereby two layers with different properties form at the front and rear of absorbers is a critical challenge in the field of kesterite thin-film solar cells, which imposes additional nonradiative recombination in the quasi-neutral region and potential limitation to the transport of hole carriers. Herein, an effective model for growing monolayer CZTSe thin-films based on metal precursors with large grains spanning the whole film is developed. Voids and fine grain layer are avoided successfully by suppressing the formation of a Sn-rich liquid metal phase near Mo back contact during alloying, while grain coarsening is greatly promoted by enhancing mass transfer during grain growth. The desired morphology exhibits several encouraging features, including significantly reduced recombination in the quasi-neutral region that contributes to the large increase of short-circuit current, and a quasi-Ohmic back contact which is a prerequisite for high fill factor. Though this growth mode may introduce more interfacial defects which require further modification, the strategies demonstrated remove a primary obstacle toward higher efficiency kesterite solar cells, and can be applicable to morphology control with other emerging chalcogenide thin films.

10.3% Efficient Green Cd-Free Cu2 ZnSnS4 Solar Cells Enabled by Liquid-Phase Promoted Grain Growth.

Small grain size and near-horizontal grain boundaries are known to be detrimental to the carrier collection efficiency and device performance of pure-sulfide Cu2 ZnSnS4 (CZTS) solar cells. However, forming large grains spanning the absorber layer while maintaining high electronic quality is challenging particularly for pure sulfide CZTS. Herein, a liquid-phase-assisted grain growth (LGG) model that enables the formation of large grains spanning across the CZTS absorber without compromising the electronic quality is demonstrated. By introducing a Ge-alloyed CZTS nanoparticle layer at the bottom of the sputtered precursor, a Cu-rich and Sn-rich liquid phase forms at the high temperature sulfurization stage, which can effectively remove the detrimental near-horizontal grain boundaries and promote grain growth, thus greatly improving the carrier collection efficiency and reducing nonradiative recombination. The remaining liquid phase layer at the rear interface shows a high work function, acting as an effective hole transport layer. The modified morphology greatly increases the short-circuit current density and fill factor, enabling 10.3% efficient green Cd-free CZTS devices. This work unlocks a grain growth mechanism, advancing the morphology control of sulfide-based kesterite solar cells.

Enhanced sensitivity of dilute aqueous adrenaline solution with an asymmetric hexagonal ring structure in the terahertz frequencies.

Quantitative detection of neurotransmitters in aqueous environment is crucial for the early diagnosis of many neurological disorders. Terahertz waves, as a non-contact and non-labeling tool, have demonstrated large potentials in quantitative biosensing. Although the detection of trace-amount analyte has been achieved with terahertz metamaterials in the recent decades, most studies have been focused on dried samples. Here, a hexagonal asymmetric metamaterial sensor was designed and fabricated for aqueous solution sensing with terahertz waves in the reflection geometry. An absorption enhancement of 43 was determined from the simulation. Dilute adrenaline solutions ranging from 30 µM to 0.6 mM were measured on our sensor using a commercial terahertz time-domain spectroscopy system, and the effective absorption was found to be linearly correlated with the concentration (R2 = 0.81). Furthermore, we found that as the concentration becomes higher (>0.6 mM), a non-linear relationship starts to take place, which confirmed the previous theory on the extended solvation shell that can be probed on the picosecond scale. Our sensor, without the need of high-power and stable terahertz sources, has enabled the detection of subtle absorption changes induced by the solvation dynamics.

Deciphering essential cistromes using genome-wide CRISPR screens.

Although millions of transcription factor binding sites, or cistromes, have been identified across the human genome, defining which of these sites is functional in a given condition remains challenging. Using CRISPR/Cas9 knockout screens and gene essentiality or fitness as the readout, we systematically investigated the essentiality of over 10,000 FOXA1 and CTCF binding sites in breast and prostate cancer cells. We found that essential FOXA1 binding sites act as enhancers to orchestrate the expression of nearby essential genes through the binding of lineage-specific transcription factors. In contrast, CRISPR screens of the CTCF cistrome revealed 2 classes of essential binding sites. The first class of essential CTCF binding sites act like FOXA1 sites as enhancers to regulate the expression of nearby essential genes, while a second class of essential CTCF binding sites was identified at topologically associated domain (TAD) boundaries and display distinct characteristics. Using regression methods trained on our screening data and public epigenetic profiles, we developed a model to predict essential cis-elements with high accuracy. The model for FOXA1 essentiality correctly predicts noncoding variants associated with cancer risk and progression. Taken together, CRISPR screens of cis-regulatory elements can define the essential cistrome of a given factor and can inform the development of predictive models of cistrome function.

Can China's carbon trading policy help achieve Carbon Neutrality? - A study of policy effects from the Five-sphere Integrated Plan perspective.

The carbon trading policy seeks to control carbon emissions by putting a price on carbon emissions and establishing a corresponding carbon market for trading. It is a significant move by China to address climate issues and achieve its Carbon Neutrality target. Therefore, assessing the policy effects of carbon trading is fundamental to its implementation nationwide. Based on the panel data of 30 provinces and cities in China from 2008 to 2018, this paper uses the Synthetic Control Method and Differences-in-Differences method to assess the effects of carbon trading policy on achieving Carbon Neutrality. By measuring the net carbon emissions, this research explores the level of Carbon Neutrality in each region. Based on the Five-sphere Integrated Plan (which covers the economy, politics, culture, social and ecological civilization), this research further verifies the impact paths of carbon trading policy on Carbon Neutrality. The results show that: First, carbon trading policy has a significant and sustainable effect on Carbon Neutrality. Second, from the perspective of the Five-sphere Integrated Plan, the carbon trading policy can help to reduce carbon sources and increase carbon sinks by adjusting the industrial structure, coordinating low-carbon policies, promoting cultural dissemination, increasing green space construction, and reducing energy intensity to achieve Carbon Neutrality. Third, cultural construction plays the most significant role in mediating carbon trading and Carbon Neutrality, followed by political construction.

Mechanical Tension-Stress in Alveolar Cleft Repaired With Autogenous Bone in Canine Models.

OBJECTIVE: Cleft lip and/or palate is a common birth defect worldwide, always accompanied by alveolar cleft. However, the success rate of secondary alveolar bone grafting is unsatisfactory. Rapid maxillary expansion (RME) often used after bone transplantation provides functional stimulation for bone graft area. This study aimed to investigate the effect of RME force on the bone graft area and midpalatal suture, and screen out the most suitable loaded force and loaded teeth, so as to provide a reference for clinical treatment. METHODS: Fourteen 24-week-old male beagles were assigned randomly to 3 groups: blank control, autogenous, and autogenous with RME. Three-dimensional finite element analysis was conducted to evaluate the distribution and value of the stress in the model. The maxillae were collected and subjected to radiography and helical computed tomography to evaluate new bone formation in the graft area. Van Gieson's Picrofuchsin staining was performed for histomorphological observation. RESULTS: After 8 weeks of RME treatment, new bone formation of the dogs was markedly accelerated, and bone resorption was significantly reduced compared with the untreated dogs or those only treated with autogenous iliac bone. The treatment with RME evidently made the bone trabecula more abundant and the area of bone formation larger. Three-dimensional finite element analysis showed that the clinical effect can be achieved by using canine teeth as the loaded teeth and applying force of 10 MPa. CONCLUSION: Rapid maxillary expansion after bone grafting had a positive effect on osteogenesis in a canine model of alveolar cleft.

ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit.

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.