Biology subjects

Zhu, Y.

Publications and source records attributed to Zhu, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2018

Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study

BackgroundExposure to \"early life\" adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.\n\nMethodsUsing a two-stage structured life course modeling approach (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing, and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776).\n\nResultsAfter covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS of lifetime exposure (vs. no exposure) failed to detect these associations.\n\nConclusionsThe developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to \"early life\" adversity may dilute observed effects.

genetics↗

bioRxiv2018

Loss of SDHB reprograms energy metabolisms and inhibits high fat diet induced metabolic syndromes

Mitochondrial respiratory complex II utilizes succinate, key substrate of the Krebs cycle, for oxidative phosphorylation, which is essential for glucose metabolism. Mutations of complex II cause cancers and mitochondrial diseases, raising a critical question of the (patho-)physiological functions. To address the fundamental role of complex II in systemic energy metabolism, we specifically knockout SDHB in mice liver, a key complex II subunit that tethers the catalytic SDHA subunit and transfers the electrons to ubiquinone, and found that SHDB deficiency abolishes the assembly of complex II without affecting other respiration complexes while largely retaining SDHA stability. SHDB ablation reprograms energy metabolism and hyperactivates the glycolysis, Krebs cycle and {beta}-oxidation pathways, leading to catastrophic energy deficit and early death. Strikingly, sucrose supplementation or high fat diet resumes both glucose and lipid metabolism and prevent early death. Also, SDHB deficient mice are completely resistant to high fat diet induced obesity. Our findings reveal that the unanticipated role of complex II orchestrating both lipid and glucose metabolisms, and suggest that SDHB is an ideal therapeutic target for combating obesity.

molecular biology↗

bioRxiv2018

USP7 cooperates with NOTCH1 to drive the oncogenic transcriptionalprogram in T cell leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Treatments1-6 show high response rates but have debilitating effects and carry risk of relapse5,7,8. Previous work implicated NOTCH1 and other oncogenes1,2,9-20. However, direct inhibition of these pathways affects healthy tissues and cancer alike. Here, we demonstrate that ubiquitin-specific protease 7 (USP7)21-32 controls leukemia growth by stabilizing the levels of the NOTCH1 and JMJD3 demethylase. USP7 is overexpressed T-ALL and is transcriptionally regulated by NOTCH1. In turn, USP7 controls NOTCH1 through deubiquitination. USP7 is bound to oncogenic targets and controls gene expression through H2B ubiquitination and H3K27me3 changes via stabilization of NOTCH1 and JMJD3. We also show that USP7 and NOTCH1 bind T-ALL superenhancers, and USP7 inhibition alters associated gene activity. These results provide a new model for deubiquitinase activity through recruitment to oncogenic chromatin loci and regulation of both oncogenic transcription factors and chromatin marks to promote leukemia. USP7 inhibition33 significantly blocked T-ALL cell growth in vitro and in vivo. Our studies also show that USP7 is upregulated in the aggressive high-risk cases of T-ALL and suggest that USP7 expression might be a prognostic marker in ALL and its inhibition could be a therapeutic tool against aggressive leukemia.

cancer biology↗

bioRxiv2017

VlbZIP30 of grapevine functions in drought tolerance via the abscisic acid core signaling pathway

Drought stress limits the growth and development of grapevines, thereby reducing productivity, but the mechanisms by which grapevines respond to drought stress remain largely uncharacterized. Here, we characterized a group A bZIP gene from Kyoho grapevine, VlbZIP30, which was shown to be induced by abscisic acid (ABA) and dehydration stress. Overexpression of VlbZIP30 in transgenic Arabidopsis enhanced dehydration tolerance during seed germination, and in the seedling and adult stages. Transcriptome analysis revealed that a major proportion of ABA- and/or drought-responsive genes are transcriptionally regulated by VlbZIP30 during ABA or mannitol treatment at the cotyledon greening stage. We identified an A. thaliana G-box motif (CACGTG) and a potential grapevine G-box motif (MCACGTGK) in the promoters of the 39 selected A. thaliana genes up-regulated in the transgenic plants and in the 35 grapevine homologs, respectively. Subsequently, using two grapevine-related databases, we found that 74% and 84% (a total of 27 genes) of the detected grapevine genes were significantly up-regulated by ABA and drought stress, respectively, suggesting that these 27 genes involve in ABA or dehydration stress and may be regulated by VlbZIP30 in grapevine. We propose that VlbZIP30 functions as a positive regulator of drought-responsive signaling in the ABA core signaling pathway.\n\nHighlightVlbZIP30 positively regulate plant drought tolerance through regulated the expression of 27 grapevine candidate genes via G-box cis-element (MCACGTGK) in ABA signaling pathway.

plant biology↗

bioRxiv2017

UV-Induced Keratin 1 Proteolysis Mediates UV-Induced Skin Damage

Keratins play critical roles in intermediate filament formation, inflammatory responses and cellular signaling in epithelium. While keratins is a major epidermal fluorophore, the mechanisms underlying the autofluorescence (AF) of keratins and its biomedical implications have remained unknown. Our study used mouse skin as a model to study these topics, showing that UV dose-dependently induced increases in green AF at the spinous layer of the epidermis of mouse within 6 hr of the UV exposures, which may be used for non-invasive prediction of UV-induced skin damage. The UV-induced AF appears to be induced by cysteine protease-mediated keratin 1 proteolysis: 1) UV rapidly induced significant keratin 1 degradation; 2) administration of keratin 1 siRNA largely decreased the UV-induced AF; and 3) administration of E-64, a cysteine protease inhibitor, significantly attenuated the UV-induced AF and keratin 1 degradation. Our study has also suggested that the UV-induced keratin 1 proteolysis may be a novel crucial pathological factor in UV-induced skin damage, which is supported by both the findings that indicate critical biological roles of keratin 1 in epithelium and our observation that prevention of UV-induced keratin 1 proteolysis can lead to decreased UV-induced skin damage. Collectively, our study has suggested that UV-induced keratin 1 proteolysis may be a novel and valuable target for diagnosis, prevention and treatment of UV-induced skin damage.

pathology↗

bioRxiv2017

A Rice Dual-localized Pentatricopeptide Repeat Protein is involved in Organellar RNA Editing with MORFs

Flowering plants engage in diverse RNA editing events in mitochondrion and chloroplast on post-transcriptional process. Although several PPRs and MORFs were identified as RNA editing factors, the underlying mechanism of PPRs and the cooperation among them are still obscure. Here, we identified a rice dual-localized PPR mutant Ospgl1. Loss-of-function of OsPGLl resulted in defect of chloroplast RNA editing at ndhD-878 and mitochondrial RNA editing at ccmFc-543, which can be restored via complementary validation. Despite the synonymous editing on ccmFc-543, loss of editing at ndhD-878 caused failure of conversion from serine to leucine, leading to the dysfunction of chloroplast and defective in photosynthetic complex, further studies demonstrated OsPGL1 directly bound to both two transcripts. The interaction between three MORFs (MORF2/8/9) and OsPGL1 were confirmed in vitro and in vivo, implied OsPGL1 functioned on RNA editing via an editosome. It also suggested MORFs assisted and contributed to the flexible PPR-RNA recognition model during RNA editing through the cooperation with PPRs. These results provide new insight into the relationship between RNA editing and plant development on chloroplast.\n\nHighlightWe firstly characterized a dual-localized PPR protein which is required for RNA editing in mitochondrion and chloroplast simultaneously. OsPGL1 binds to two distinguish target transcripts directly and cooperated with MORFs.

molecular biology↗

bioRxiv2017

Neural code subserving feed-forward inhibition in a collision detection circuit

Feed-forward inhibition is ubiquitous as a motif in the organization of neuronal circuits. During sensory information processing, it is traditionally thought to sharpen the responses and temporal tuning of feed-forward excitation onto principal neurons. As it often exhibits complex time-varying activation properties, feed-forward inhibition could also convey information used by single neurons to implement dendritic computations on sensory stimulus variables. We investigated this possibility in a collision detecting neuron of the locust optic lobe that receives both feed-forward excitation and inhibition. We identified a small population of neurons mediating feed-forward inhibition, with wide visual receptive fields and whose responses depend both on the size and speed of moving stimuli. By studying responses to simulated objects approaching on a collision course, we determined that they jointly encode the angular size of expansion of the stimulus. Feed-forward excitation on the other hand encodes a function of the angular velocity of expansion and the targeted collision detecting neuron combines these two variables non-linearly in its firing output. Thus, feed-forward inhibition actively contributes to the detailed firing rate time course of this collision detecting neuron, a feature critical to the appropriate execution of escape behaviors. These results suggest that feed-forward inhibition could similarly convey time-varying stimulus information in other neuronal circuits.

neuroscience↗

bioRxiv2017

Muscarinic Lateral Excitation Contributes to Visual Object Segmentation during Collision Avoidance

Visual neurons specialized in tracking objects on a collision course are often finely tuned to their target stimuli as this is critical for survival. The presynaptic neural networks converging on these neurons and their role in tuning them remains poorly understood. We took advantage of well-known characteristics of one such neuron to investigate the properties of its presynaptic input network. We find a structure more complex than hitherto realized. In addition to dynamic lateral inhibition used to filter out background motion, presynaptic circuits include normalizing inhibition and short-range lateral excitatory interactions mediated by muscarinic acetylcholine receptors. These interactions preferentially boost responses to coherently expanding visual stimuli generated by colliding objects, as opposed to spatially incoherent controls, helping implement object segmentation. Hence, in addition to active dendritic conductances within collision detecting neurons, multiple layers of both inhibitory and excitatory presynaptic connections are needed to finely tune neural circuits for collision detection.

neuroscience↗

bioRxiv2017

PRS-on-Spark: a novel, efficient and flexible approach for generating polygenic risk scores

MotivationPolygenic risk scores describe the genomic contribution to complex phenotypes and consistently account for a larger proportion of the variance than single nucleotide polymorphisms alone. However, there is little consensus on the optimal data input for generating polygenic risk scores and existing approaches largely preclude the use of imputed posterior probabilities and strand-ambiguous SNPs.\n\nResultsWe developed PRS-on-Spark (PRSoS) a polygenic risk score software implemented in Apache Spark and Python that accommodates a variety of data input (e.g., observed genotypes, imputed genotypes, or imputed posterior probabilities) and strand-ambiguous SNPs. We show that PRSoS is flexible and efficient and computes polygenic risk scores at a range of p-value thresholds more quickly than existing software (PRSice). We also show that the use of imputed posterior probabilities and the inclusion of strand-ambiguous SNPs increases the proportion of variance explained by polygenic risk scores for major depression.\n\nAvailability and ImplementationPRSoS is written in Apache Spark and Python and is freely available (see https://github.com/MeaneyLab/PRSoS).

bioinformatics↗

bioRxiv2017

Imaging-Genomics Study Of Head-Neck Squamous Cell Carcinoma: Associations Between Radiomic Phenotypes And Genomic Mechanisms Via Integration Of TCGA And TCIA

PurposeRecent data suggest that imaging radiomics features for a tumor could predict important genomic biomarkers. Understanding the relationship between radiomic and genomic features is important for basic cancer research and future patient care. For Head and Neck Squamous Cell Carcinoma (HNSCC), we perform a comprehensive study to discover the imaging-genomics associations and explore the potential of predicting tumor genomic alternations using radiomic features.\n\nMethodsOur retrospective study integrates whole-genome multi-omics data from The Cancer Genome Atlas (TCGA) with matched computed tomography imaging data from The Cancer Imaging Archive (TCIA) for the same set of 126 HNSCC patients. Linear regression analysis and gene set enrichment analysis are used to identify statistically significant associations between radiomic imaging features and genomic features. Random forest classifier is used to predict two key HNSCC molecular biomarkers, the status of human papilloma virus (HPV) and disruptive TP53 mutation, based on radiomic features.\n\nResultsWide-spread and statistically significant associations are discovered between genomic features (including miRNA expressions, protein expressions, somatic mutations, and transcriptional activities, copy number variations, and promoter region DNA methylation changes of pathways) and radiomic features characterizing the size, shape, and texture of tumor. Prediction of HPV and TP53 mutation status using radiomic features achieves an area under the receiver operating characteristics curve (AUC) of 0.71 and 0.641, respectively.\n\nConclusionOur analysis suggests that radiomic features are associated with genomic characteristics in HNSCC and provides justification for continued development of radiomics as biomarkers for relevant genomic alterations in HNSCC.

cancer biology↗

bioRxiv2017

TCGA-Assembler 2: Software Pipeline for Retrieval and Processing of TCGA/CPTAC Data

MotivationThe Cancer Genome Atlas (TCGA) program has produced huge amounts of cancer genomics data providing unprecedented opportunities for research. In 2014, we developed TCGA-Assembler (Zhu et al, 2014), a software pipeline for retrieval and processing of public TCGA data. In 2016, TCGA data were transferred from the TCGA data portal to the Genomic Data Commons (GDC), which is supported by a different set of data storage and retrieval mechanisms. In addition, new proteomics data of TCGA samples have been generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program, which were not available for downloading through TCGA-Assembler. It is desirable to acquire and integrate data from both GDC and CPTAC.\n\nResultsWe develop TCGA-Assembler 2 (TA2) to automatically download and integrate data from GDC and CPTAC. We make substantial improvement on the functionality of TA2 to enhance user experience and software performance. TA2 together with its previous version have helped more than 2,000 researchers from 64 countries to access and utilize TCGA and CPTAC data in their research. Availability of TA2 will continue to allow existing and new users to conduct reproducible research based on TCGA and CPTAC data.\n\nAvailabilityhttp://www.compgenome.org/TCGA-Assembler/\n\nContactkoaeraser@gmail.com or zhuyitan@gmail.com

bioinformatics↗

bioRxiv2017

Chronic intermittent nicotine delivery with lung alveolar region-targeted aerosol technology produces circadian blood pharmacokinetics in rats resembling human smokers

IntroductionCigarette smoke is an aerosol containing microparticles that carry nicotine into lung alveolar region where nicotine is rapidly absorbed into circulation. Nicotine exposure in smokers is a chronic intermittent process, with intake during wakefulness and abstinence during sleep resulting in circadian fluctuation of blood nicotine levels. Here we present a smoking-relevant nicotine exposure device and rodent model.\n\nMethodsWe developed a computer controlled integrated platform where freely moving rodents can be exposed to episodic nicotine aerosol on an investigator-designed schedule. Rats were exposed to nicotine aerosol once every half hr in the dark phase of 12/12-hr dark/light cycles for 10 days. Plasma nicotine and its metabolite cotinine levels were determined with a LC-MS/MS method.\n\nResultsWe characterized the aerosol in the breathing zone of the rodent exposure chamber. The droplet size distribution was within the respirable diameter range. The system can generate a wide range of nicotine concentrations in air that meet a variety of experimental needs. We optimized the parameters of aerosol generation and exposure: plasma nicotine and cotinine concentrations reached 30-35 ng/ml and 190-240 ng/ml, respectively. The nicotine levels and circadian patterns resembled the pharmacokinetic pattern of human smokers.\n\nConclusionsWe developed an aerosol system that can produce chronic intermittent nicotine exposure in unanesthetized and unrestrained rodents with route of administration and circadian blood pharmacokinetics resembling human smokers. This methodology is a novel tool for studies of behavior, pharmacology and toxicology of chronic nicotine exposure, nicotine addiction, tobacco-related diseases, teratogenicity, and for discovery of therapeutics.\n\nImplicationsWe developed a method and an alveolar region-targeted aerosol system that provides chronic intermittent nicotine exposure in rodents. The method produces clinically relevant animal models with the route of administration and circadian pharmacokinetics resembling human smokers. This method is a novel tool for understanding the health effects of chronic nicotine exposures such as with tobacco cigarettes, E-cigarettes and other tobacco products, for studies of pharmacology, toxicology, nicotine addiction, tobacco-related diseases, and for discovery of medications.

pharmacology and toxicology↗

bioRxiv2017

Development of noninvasive biomarkers of response to proteasome inhibitor therapy (ixazomib) by imaging disrupted protein homeostasis in mouse models of solid tumors

With clinically-approved proteasome inhibitors now a standard of care for multiple myeloma, and increasing interest in their use in solid tumors, methods for monitoring therapeutic response in vivo are critically required. Here, we show that tumor protein homeostasis can be noninvasively monitored, using chemical exchange (CEST) magnetic resonance imaging (MRI) as a surrogate marker for proteasome inhibition, alongside diffusion MRI and relaxometry. We show that the in vivo CEST signal associated with amides and amines increases in proportion to proteasome inhibitor dose (ixazomib) and the magnitude of therapeutic effect in colorectal cancer xenografts. Moreover, we show that SW1222 and LS174T human colorectal cancer cell lines demonstrate differing sensitivities to ixazomib, which was reflected in our MRI measurements. We also found evidence of a mild stimulation in tumor growth at low ixazomib doses. Our results therefore identify CEST MRI as a promising method for safely and noninvasively monitoring changes in tumor protein homeostasis.

biophysics↗

bioRxiv2017

Integrated analysis of DSB patterns reveals precisely DSB formation mechanisms following replication fork collapse

DNA double-strand breaks (DSBs) can be detected by label-based sequencing or pulsed-field gel electrophoresis (PFGE). Sequencing yields population-average DSB frequencies genome-wide, while PFGE reveals percentages of broken chromosomes. We constructed a mathematical framework to combine advantages of both: high-resolution DSB locations and their population distribution. We also use sequencing read patterns to identify replication-induced DSBs and active replication origins. We describe changes in spatiotemporal replication program upon hydroxyurea-induced replication stress. We found that one-ended DSBs, resulting from collapsed replication forks, are population-representative, while majority of two-ended DSBs (79-100%) are not. To study replication fork collapse, we used strains lacking the checkpoint protein Mec1 and the endonuclease Mus81 and quantified that 19% and 13% of hydroxyurea-induced one-ended DSBs are Mec1-and Mus81-dependent, respectively. We also clarified that Mus81-induced one-ended DSBs are Mec1-dependent.

genomics↗

bioRxiv2017

Quantitative DSB sequencing (qDSB-Seq): a method for genome-wide accurate estimation of absolute DNA double-strand break frequencies per cell

Sequencing-based methods for mapping DNA double-strand breaks (DSBs) allow measurement only of relative frequencies of DSBs between loci, which limits our understanding of the physiological relevance of detected DSBs. We propose quantitative DSB sequencing (qDSB-Seq), a method providing both DSB frequencies per cell and their precise genomic coordinates. We induced spike-in DSBs by a site-specific endonuclease and used them to quantify labeled DSBs (e.g. using i-BLESS). Utilizing qDSB-Seq, we determined numbers of DSBs induced by a radiomimetic drug and various forms of replication stress, and revealed several orders of magnitude differences in DSB frequencies. We also measured for the first time Top1-dependent absolute DSB frequencies at replication fork barriers. qDSB-Seq is compatible with various DSB labeling methods in different organisms and allows accurate comparisons of absolute DSB frequencies across samples.

genomics↗

bioRxiv2017

Targeting posttranslational modifications of RioK1 inhibits the progression of colorectal and gastric cancers

RioK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RioK1 is methylated at K411 by SETD7 methyltransferase, and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RioK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RioK1. FBXO6 specifically interacts with K411-methylated RioK1 through its FBA domain to induce RioK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RioK1 at T410, which stabilizes RioK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RioK1. Functional experiments demonstrate the RioK1 methylation reduces the tumor growth and metastasis in CRC and GC. Importantly, the protein levels of CK2 and LSD1 show an inverse correlation with FBXO6 and SETD7 expression in human CRC tissues. Therefore, this study highlights the importance of a RioK1 methylation-phosphorylation switch in determining CRC and GC development.

cancer biology↗

bioRxiv2017

Identification of disease resistance genes from a Chinese wild grapevine (Vitis davidii) by analysing grape transcriptomes and transgenic Arabidopsis

HighlightTranscription profiles showed that 20 candidate genes were obviously co-expressed at 12 hpi in 30 Vitis davidii.\n\nVdWRKY53 trancription factor enhanced the resisitance in grapevine and Arabidopsis.\n\nAbstractThe molecular mechanisms underlying disease tolerance in grapevines remain uncharacterized, even though there are substantial differences in the resistance of grapevine species to fungal and bacterial diseases. In this study, we identified genes and genetic networks involved in disease resistance in grapevines by comparing the transcriptomes of a strongly resistant clone of Chinese wild grapevine (Vitis davidii cv. Ciputao 941, DAC) and a susceptible clone of European grapevine (Vitis vinifera cv. Manicure Finger, VIM) before and after infection with white rot disease (Coniella diplodiella). Disease resistance-related genes were triggered in DAC approximately 12 hours post infection (hpi) with C. diplodiella. Twenty candidate resistant genes were co-expressed in DAC. One of these candidate genes, VdWRKY53 (GenBank accession KY124243), was over-expressed in transgenic Arabidopsis thaliana plants and was found to provide these plants with enhanced resistance to C. diplodiella, Pseudomonas syringae pv tomato PDC3000, and Golovinomyces cichoracearum. This result indicates that VdWRKY53 may be involved in nonspecific resistance via interaction with fungal and oomycete elicitor signals and the activation of defence gene expression. These results provide potential gene targets for molecular breeding to develop resistant grape cultivars.

molecular biology↗

bioRxiv2017

BRG1/BRM-associated factor complex subunit diversity promotes temporally distinct gene expression programs in cardiogenesis

Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation with mass spectrometry (IP-MS), we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, and identified BAF60c (SMARCD3) and BAF170 (SMARCC2) as subunits enriched in CPs and cardiomyocytes (CM). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, but in CMs control different gene expression programs, although still promoting a cardiac-specific gene set. BRG1, BAF60, and BAF170 all modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition and stoichiometry, and promote BRG1 occupancy in CM. Additionally, BAF170 facilitates expulsion of BRG1-containing complexes in the transition from CP to CM. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby directs temporal gene expression programs in cardiogenesis.\n\nSignificance statementBRG1/BRM associated factors (BAF) form multi-subunit protein complexes that reorganize chromatin and regulate transcription. Specific BAF complex subunits have important roles during cell differentiation and development. We systematically identify BAF subunit composition and find temporal enrichment of subunits during cardiomyocyte differentiation. We find the catalytic subunit BRG1 has important contributions in initiating gene expression programs in cardiac progenitors along with cardiac-enriched subunits BAF60c and BAF170. Both these proteins regulated BAF subunit composition and chromatin accessibility and prevent expression of non-cardiac developmental genes during precursor to cardiomyocyte differentiation. Mechanistically, we find BAF170 destabilizes the BRG1 complex and expels BRG1 from cardiomyocyte-specific genes. Thus, our data shows synergies between diverse BAF subunits in facilitating temporal gene expression programs during cardiogenesis.

developmental biology↗