scholarly journals Chromatin structure changes in Daphnia populations upon exposure to environmental cues – or – The discovery of Wolterecks “Matrix”

2020 ◽  
Author(s):  
Ronaldo de Carvalho AUGUSTO ◽  
Aki Minoda ◽  
Oliver Rey ◽  
Celine Cosseau ◽  
Cristian Chaparro ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Chromatin Structure ◽  
Biological Material ◽  
Morphological Changes ◽  
Daphnia Pulex ◽  
Experimental System ◽  
Control Treatment ◽  
Open Chromatin ◽  
Structure Changes ◽  
Genome Wide

Abstract Background: This study therefore describes the classical experimental system postulated by Richard Woltereck 100 years ago: the adaptive morphological phenotypic plasticity of daphnia . Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the adaptation of organisms exposed to an environmental stimulus and it is increasingly related to epigenetic mechanisms. Several studies have started to identify the epigenetic basis of phenotypic plasticity of daphnia including non-coding RNAs, covalent modifications at the histone tails and DNA methylation however no study has yet investigated those effect on the genome-wide chromatin structure. The aim of this work was to study for the first time the overall genome-wide chromatin structure of Daphnia pulex in the context of the iconic complex defense response to predation. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues.Results: Our results encouraged the expected induction of anti-predatory morphological changes in the stress treatment was significantly higher than that of daphnia from the control treatment. The developed ATAC-seq technique can be used to characterize chromatin structures of individuals even those that are small and thus with few biological material, making it possible to determine epigenetic polymorphisms relatively easily and at reasonable cost in full populations. In addition, we deliver evidence that chromatin structure changes upon stimuli from the environment.Conclusion: We report here an extremely fast and straightforward method to map the chromatin status of individuals using small amounts of input biological material. W e show here that changes in the environment, such as predator presence the chromatin structure is profoundly reorganised confirming Woltereck ’s classical postulate.

scholarly journals Chromatin structure changes in Daphnia populations upon exposure to environmental cues – or – The discovery of Wolterecks “Matrix”

2019 ◽  
Author(s):  
Ronaldo de Carvalho Augusto ◽  
Aki Minoda ◽  
Oliver Rey ◽  
Céline Cosseau ◽  
Cristian Chaparro ◽  
...  
Keyword(s):  
Phenotypic Plasticity ◽  
Chromatin Structure ◽  
Environmental Gradients ◽  
Gene Mutations ◽  
Reaction Norms ◽  
Environmental Cues ◽  
Global Changes ◽  
Open Chromatin ◽  
Norm Of Reaction ◽  
Structure Changes

AbstractPhenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20th century by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as “norm of reaction”. Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-flee daphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called the Matrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Woltereck’s classical experiments with daphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Woltereck’s classical postulate.

scholarly journals Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

2018 ◽  
Vol 14 (11) ◽  
pp. 1571-1585 ◽  
Author(s):  
Mengnan He ◽  
Yan Li ◽  
Qianzi Tang ◽  
Diyan Li ◽  
Long Jin ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
Structure Changes ◽  
Genome Wide

scholarly journals Strong replicators associated with open chromatin are sufficient to establish an early replicating domain

2018 ◽  
Author(s):  
Caroline Brossas ◽  
Sabarinadh Chilaka ◽  
Antonin Counillon ◽  
Marc Laurent ◽  
Coralie Goncalves ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
Binding Sites ◽  
Replication Origin ◽  
Molecular Mechanisms ◽  
Open Chromatin ◽  
Strongly Correlated ◽  
Topologically Associating Domains ◽  
Genome Wide ◽  
Close Physical Proximity ◽  
Temporal Program

AbstractVertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into topologically associating domains. However, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late replicating region for earlier replication. When inserted side-by-side, these modules acted in cooperation, with similar effects on two late-replicating regions. Targeted insertions of these two modules at two chromosomal sites separated by 30 kb brought these two modules into close physical proximity and induced the formation of an early-replicating domain. Thus, combinations of strong origins and cis-elements capable of opening the chromatin structure are the basic units of early-replicating domains, and are absent from late-replicated regions. These findings are consistent with those of genome-wide studies mapping strong initiation sites and open chromatin marks in vertebrate genomes.

The relationship between higher-order chromatin structure and transcription

2006 ◽  
Vol 73 ◽  
pp. 59-66 ◽  
Author(s):  
Nick Gilbert ◽  
Wendy A. Bickmore
Keyword(s):  
Chromatin Structure ◽  
Sucrose Gradient ◽  
Gene Density ◽  
Open Chromatin ◽  
Genome Wide ◽  
Silent Genes ◽  
High Gene ◽  
The Relationship ◽  
High Gene Density ◽  
Active Genes

It has generally been assumed that transcriptionally active genes are in an ‘open’ chromatin structure and that silent genes have a ‘closed’ chromatin structure. Here we re-assess this axiom in the light of genome-wide studies of chromatin fibre structure. Using a combination of sucrose gradient sedimentation and genomic microarrays of the human genome, we argue that open chromatin fibres originate from regions of high gene density, whether or not those genes are transcriptionally active.

scholarly journals Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tejaswi Iyyanki ◽  
Baozhen Zhang ◽  
Qixuan Wang ◽  
Ye Hou ◽  
Qiushi Jin ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Cancer Cell ◽  
Genome Structure ◽  
Transcription Factor Binding ◽  
Specific Gene ◽  
Open Chromatin ◽  
Factor Binding ◽  
3D Genome ◽  
Genome Wide

Abstract Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARG are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3, and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remain unknown. Result We determine the genome-wide transcriptome, enhancer landscape, and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype.

scholarly journals Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Thomas A. Johnson ◽  
Ville Paakinaho ◽  
Sohyoung Kim ◽  
Gordon L. Hager ◽  
Diego M. Presman
Keyword(s):  
Receptor Binding ◽  
Site Response ◽  
Physiological Role ◽  
Binding Potential ◽  
Open Chromatin ◽  
Imaging Data ◽  
Response Elements ◽  
Genome Wide ◽  
Genomic Studies

AbstractA widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.

scholarly journals The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilona E. Grabowicz ◽  
Bartek Wilczyński ◽  
Bożena Kamińska ◽  
Adria-Jaume Roura ◽  
Bartosz Wojtaś ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Genetic Alterations ◽  
Chromatin Organization ◽  
Open Chromatin ◽  
Low Grade ◽  
Strong Impact ◽  
Cell Matrix ◽  
Topologically Associating Domains ◽  
Genome Wide

AbstractGenome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.

scholarly journals Chromatin architectural proteins regulate flowering time by precluding gene looping

2021 ◽  
Vol 7 (24) ◽  
pp. eabg3097
Author(s):  
Bo Zhao ◽  
Yanpeng Xi ◽  
Junghyun Kim ◽  
Sibum Sung
Keyword(s):  
Chromatin Structure ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Evolutionarily Conserved ◽  
Architectural Proteins ◽  
Floral Repressor ◽  
Flanking Regions ◽  
Genome Wide Study

Chromatin structure is critical for gene expression and many other cellular processes. In Arabidopsis thaliana, the floral repressor FLC adopts a self-loop chromatin structure via bridging of its flanking regions. This local gene loop is necessary for active FLC expression. However, the molecular mechanism underlying the formation of this class of gene loops is unknown. Here, we report the characterization of a group of linker histone-like proteins, named the GH1-HMGA family in Arabidopsis, which act as chromatin architecture modulators. We demonstrate that these family members redundantly promote the floral transition through the repression of FLC. A genome-wide study revealed that this family preferentially binds to the 5′ and 3′ ends of gene bodies. The loss of this binding increases FLC expression by stabilizing the FLC 5′ to 3′ gene looping. Our study provides mechanistic insights into how a family of evolutionarily conserved proteins regulates the formation of local gene loops.

scholarly journals Intricate genetic programs controlling dormancy in Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Abrar A. Abidi ◽  
Eliza J. R. Peterson ◽  
Mario L. Arrieta-Ortiz ◽  
Boris Aguilar ◽  
James T. Yurkovich ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Time Course ◽  
Experimental System ◽  
Topology Analysis ◽  
Transcriptional Dynamics ◽  
Regulatory Circuits ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Location Map ◽  
Favorable Conditions

AbstractMycobacterium tuberculosis (MTB), responsible for the deadliest infectious disease worldwide, displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and opportunistically exploit immunocompromised individuals. Uncovering the gene regulatory programs that underlie the dramatic phenotypic shifts in MTB during disease latency and reactivation has posed an extraordinary challenge. We developed a novel experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the chain of transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding location map and insights from network topology analysis, we identified regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions.One Sentence SummaryHigh-resolution transcriptional time-course reveals six-state genetic program that enables MTB to enter and exit hypoxia-induced dormancy.

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