scholarly journals A nutriepigenetic pathway links nutrient information to sensory plasticity

2021 ◽  
Author(s):  
Anoumid Vaziri ◽  
Daniel Wilinski ◽  
Peter Freddolino ◽  
Carrie Ferrario ◽  
MONICA DUS
Keyword(s):  
Behavioral Plasticity ◽  
Sweet Taste ◽  
Chromatin Accessibility ◽  
Metabolic Enzyme ◽  
Lingual Epithelium ◽  
Chromatin Dynamics ◽  
Brain Physiology ◽  
Taste Changes ◽  
Sensory Plasticity ◽  
Dietary Sugar

Diet composition has a profound influence on brain physiology and behavior, but the mechanisms through which nutrient information is transmuted into neural changes remain elusive. Here we uncover how the metabolic enzyme O-GlcNAc Transferase (OGT) transforms information about the dietary environment into taste adaptations. We show that in the fly D. melanogaster, OGT decorates the chromatin of the sweet taste neurons and provides the nutrient context to drive changes in chromatin accessibility in response to high dietary sugar. Specifically, we found that OGT cooperates with the epigenetic silencer Polycomb Repressive Complex 2.1 (PRC2.1) to promote nutrient-sensitive variations in chromatin openness; these chromatin dynamics result in changes in gene expression and taste plasticity that are dependent on the catalytic activity of OGT. Parallel nutrigenomic signatures were also observed in the lingual epithelium of rats exposed to high dietary sugar, suggesting that this conserved metabolic-epigenetic pathway may also underlie diet-dependent taste changes in mammals. Together our findings reveal a novel role for nutriepigenetic signaling in the brain: amplifying nutrient perturbations into robust changes in chromatin accessibility and transcriptional output that shape neural and behavioral plasticity.

scholarly journals Chromatin dynamics during hematopoiesis reveal discrete regulatory modules instructing differentiation

2020 ◽  
Author(s):  
Grigorios Georgolopoulos ◽  
Mineo Iwata ◽  
Nikoletta Psatha ◽  
Andrew Nishida ◽  
Tannishtha Som ◽  
...  
Keyword(s):  
Temporal Dynamics ◽  
Ex Vivo ◽  
Chromatin Accessibility ◽  
Dnase I ◽  
Lineage Commitment ◽  
Gene Promoters ◽  
Chromatin Dynamics ◽  
Regulatory Modules ◽  
Hypersensitive Sites ◽  
Regulatory Landscape

AbstractLineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis illuminates the fine-scale temporal dynamics of these regulatory modules during lineage-resolution between these two fates. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.

scholarly journals ASC proneural transcription factors mediate the timely initiation of the neural program during neuroectodermal to neuroblast transition ensuring progeny fidelity

2021 ◽  
Author(s):  
Vasiliki Theodorou ◽  
Aikaterini Stefanaki ◽  
Minas Drakos ◽  
Dafne Triantafyllou ◽  
Christos Delidakis
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Cis Elements ◽  
Enhancer Activity ◽  
Timely Initiation ◽  
Chromatin Dynamics ◽  
Neural Fate ◽  
Neural Specification

Background: ASC/ASCL proneural transcription factors are oncogenic and exhibit impressive reprogramming and pioneer activities. In both Drosophila and mammals, these factors are central in the early specification of the neural fate, where they act in opposition to Notch signalling. However, the role of ASC on the chromatin during CNS neural stem cells birth remains elusive. Results: We investigated the chromatin changes accompanying neural commitment using an integrative genetics and genomics methodology. We found that ASC factors bind equally strongly to two distinct classes of cis-regulatory elements: open regions remodeled earlier during maternal to zygotic transition by Zelda and Zelda-independent, less accessible regions. Both classes cis-elements exhibit enhanced chromatin accessibility during neural specification and correlate with transcriptional regulation of genes involved in many biological processes necessary for neuroblast function. We identified an ASC-Notch regulated TF network that most likely act as the prime regulators of neuroblast function. Using a cohort of ASC target genes, we report that ASC null neuroblasts are defectively specified, remaining initially stalled, lacking expression of many proneural targets and unable to divide. When they eventually start proliferating, they produce compromised progeny. Generation of lacZ reporter lines driven by proneural-bound elements display enhancer activity within neuroblasts and proneural dependency. Therefore, the partial neuroblast identity seen in the absence of ASC genes is driven by other, proneural-independent, cis-elements. Neuroblast impairment and the late differentiation defects of ASC mutants are corrected by ectodermal induction of individual ASC genes but not by individual members of the TF network downstream of ASC. However, in wild type embryos induction of individual members of this network induces CNS hyperplasia, suggesting that they synergize with the activating function of ASC to establish the chromatin dynamics that promote neural specification. Conclusion: ASC factors bind a large number of enhancers to orchestrate the timely activation of the neural chromatin program during neuroectodermal to neuroblast transition. This early chromatin remodeling is crucial for both neuroblast homeostasis as well as future progeny fidelity.

scholarly journals An atlas of dynamic chromatin landscapes in mouse fetal development

Nature ◽  
2020 ◽  
Vol 583 (7818) ◽  
pp. 744-751 ◽  
Author(s):  
David U. Gorkin ◽  
Iros Barozzi ◽  
Yuan Zhao ◽  
Yanxiao Zhang ◽  
Hui Huang ◽  
...  
Keyword(s):  
Fetal Development ◽  
Target Genes ◽  
Developmental Stages ◽  
Chromatin Accessibility ◽  
Chromatin State ◽  
Mammalian Development ◽  
Mouse Fetus ◽  
Chromatin Dynamics ◽  
Mouse Tissues ◽  
Genomic Resource

AbstractThe Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus. In total we performed 1,128 chromatin immunoprecipitation with sequencing (ChIP–seq) assays for histone modifications and 132 assay for transposase-accessible chromatin using sequencing (ATAC–seq) assays for chromatin accessibility across 72 distinct tissue-stages. We used integrative analysis to develop a unified set of chromatin state annotations, infer the identities of dynamic enhancers and key transcriptional regulators, and characterize the relationship between chromatin state and accessibility during developmental gene regulation. We also leveraged these data to link enhancers to putative target genes and demonstrate tissue-specific enrichments of sequence variants associated with disease in humans. The mouse ENCODE data sets provide a compendium of resources for biomedical researchers and achieve, to our knowledge, the most comprehensive view of chromatin dynamics during mammalian fetal development to date.

scholarly journals Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Gregory Smutzer ◽  
Roni K. Devassy
Keyword(s):  
Oral Cavity ◽  
Sweet Taste ◽  
Sensory Cells ◽  
Lingual Epithelium ◽  
Calcium Dependent ◽  
Health And Nutrition ◽  
Inositol Phospholipids ◽  
Trpv1 Receptors ◽  
Increased Sensitivity ◽  
Psychophysical Studies

Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.

scholarly journals Effective Dynamics of Nucleosome Configurations at the Yeast PHO5 Promoter

2020 ◽  
Author(s):  
Michael Roland Wolff ◽  
Andrea Schmid ◽  
Philipp Korber ◽  
Ulrich Gerland
Keyword(s):  
Single Molecule ◽  
Chromatin Accessibility ◽  
State Transitions ◽  
Chromatin Dynamics ◽  
New Class ◽  
Nucleosome Dynamics ◽  
Effective Dynamics ◽  
Global And Local ◽  
Chromatin Opening

AbstractChromatin dynamics are mediated by remodeling enzymes and play crucial roles in gene regulation, as established in a paradigmatic model, the yeast PHO5 promoter. However, effective nucleosome dynamics, i.e. trajectories of promoter nucleosome configurations, remain elusive. Here, we infer such dynamics from the integration of published single-molecule data that capture multi-nucleosome configurations for repressed to fully active PHO5 promoter states with other existing histone turnover and new chromatin accessibility data. We devised and systematically investigated a new class of “regulated on-off-slide” models simulating global and local nucleosome (dis)assembly and sliding. Only seven of 68 145 models agreed well with all data. All seven models involve sliding and the known central role of the N-2 nucleosome, but regulate promoter state transitions by modulating just one assembly rather than disassembly process. This is consistent with but challenges common interpretations of previous observations at the PHO5 promoter and suggests chromatin opening by binding competitions.

scholarly journals Improved single-cell ATAC-seq reveals chromatin dynamics of in vitro corticogenesis

2019 ◽  
Author(s):  
Ryan M. Mulqueen ◽  
Brooke A. DeRosa ◽  
Casey A. Thornton ◽  
Zeynep Sayar ◽  
Kristof A. Torkenczy ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Networks ◽  
Regulatory Gene ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Chromatin Dynamics ◽  
Cell Library ◽  
Fate Decision

AbstractDevelopment is a complex process that requires the precise modulation of regulatory gene networks controlled through dynamic changes in the epigenome. Single-cell-omic technologies provide an avenue for understanding the mechanisms of these processes by capturing the progression of epigenetic cell states during the course of cellular differentiation using in vitro or in vivo models1. However, current single-cell epigenomic methods are limited in the information garnered per individual cell, which in turn limits their ability to measure chromatin dynamics and state shifts. Single-cell combinatorial indexing (sci-) has been applied as a strategy for identifying single-cell-omic originating libraries and removes the necessity of single-cell, single-compartment chemistry2. Here, we report an improved sci-assay for transposase accessible chromatin by sequencing (ATAC-seq), which utilizes the small molecule inhibitor Pitstop 2™ (scip-ATAC-seq)3. We demonstrate that these improvements, which theoretically could be applied to any in situ transposition method for single-cell library preparation, significantly increase the ability of transposase to enter the nucleus and generate highly complex single-cell libraries, without altering biological signal. We applied sci-ATAC-seq and scip-ATAC-seq to characterize the chromatin dynamics of developing forebrain-like organoids, an in vitro model of human corticogenesis4. Using these data, we characterized novel putative regulatory elements, compared the epigenome of the organoid model to human cortex data, generated a high-resolution pseudotemporal map of chromatin accessibility through differentiation, and measured epigenomic changes coinciding with a neurogenic fate decision point. Finally, we combined transcription factor motif accessibility with gene activity (GA) scores to directly observe the dynamics of complex regulatory programs that regulate neurogenesis through developmental pseudotime. Overall, scip-ATAC-seq increases information content per cell and bolsters the potential for future single-cell studies into complex developmental processes.

scholarly journals Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

2016 ◽  
Author(s):  
Aaron C. Daugherty ◽  
Robin Yeo ◽  
Jason D. Buenrostro ◽  
William J. Greenleaf ◽  
Anshul Kundaje ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Developmental Stages ◽  
Model Organism ◽  
High Sensitivity ◽  
Chromatin Accessibility ◽  
Chromatin Dynamics ◽  
C Elegans ◽  
Crucial Component ◽  
Organismal Development

AbstractChromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism C. elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5,000 distal non-coding regions exhibit dynamic changes in chromatin accessibility between developmental stages, and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type-and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.

scholarly journals Chromatin Dynamics and Gene Expression Response to Heat Exposure in Field-Conditioned versus Laboratory-Cultured Nematostella vectensis

2021 ◽  
Vol 22 (14) ◽  
pp. 7454
Author(s):  
Eviatar Weizman ◽  
Mieka Rinsky ◽  
Noa Simon-Blecher ◽  
Sarit Lampert-Karako ◽  
Orly Yaron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acid Metabolism ◽  
Heat Exposure ◽  
Chromatin Accessibility ◽  
Nematostella Vectensis ◽  
Rna Seq ◽  
Short Term ◽  
Gene Expression Response ◽  
Chromatin Dynamics ◽  
Expression Response

Organisms’ survival is associated with the ability to respond to natural or anthropogenic environmental stressors. Frequently, these responses involve changes in gene regulation and expression, consequently altering physiology, development, or behavior. Here, we present modifications in response to heat exposure that mimics extreme summertime field conditions of lab-cultured and field-conditioned Nematostella vectensis. Using ATAC-seq and RNA-seq data, we found that field-conditioned animals had a more concentrated reaction to short-term thermal stress, expressed as enrichment of the DNA repair mechanism pathway. By contrast, lab animals had a more diffuse reaction that involved a larger number of differentially expressed genes and enriched pathways, including amino acid metabolism. Our results demonstrate that pre-conditioning affects the ability to respond efficiently to heat exposure in terms of both chromatin accessibility and gene expression and reinforces the importance of experimentally addressing ecological questions in the field.

scholarly journals MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1

2017 ◽  
Vol 216 (9) ◽  
pp. 2715-2729 ◽  
Author(s):  
Ann-Christin Hau ◽  
Britta Moyo Grebbin ◽  
Zsuzsa Agoston ◽  
Marie Anders-Maurer ◽  
Tamara Müller ◽  
...  
Keyword(s):  
Cell Fate ◽  
Integration Site ◽  
Control Cell ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Chromatin Dynamics ◽  
Cell Fate Decisions ◽  
Sequence Of Events ◽  
Undifferentiated Cells ◽  
Mechanistic Basis

Pre–B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site (MEIS) proteins control cell fate decisions in many physiological and pathophysiological contexts, but how these proteins function mechanistically remains poorly defined. Focusing on the first hours of neuronal differentiation of adult subventricular zone–derived stem/progenitor cells, we describe a sequence of events by which PBX-MEIS facilitates chromatin accessibility of transcriptionally inactive genes: In undifferentiated cells, PBX1 is bound to the H1-compacted promoter/proximal enhancer of the neuron-specific gene doublecortin (Dcx). Once differentiation is induced, MEIS associates with chromatin-bound PBX1, recruits PARP1/ARTD1, and initiates PARP1-mediated eviction of H1 from the chromatin fiber. These results for the first time link MEIS proteins to PARP-regulated chromatin dynamics and provide a mechanistic basis to explain the profound cellular changes elicited by these proteins.

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