Systematic mapping of chromatin state landscapes during mouse development

SUMMARYEmbryogenesis requires epigenetic information that allows each cell to respond appropriately to developmental cues. Histone modifications are core components of a cell’s epigenome, giving rise to chromatin states that modulate genome function. Here, we systematically profile histone modifications in a diverse panel of mouse tissues at 8 developmental stages from 10.5 days post conception until birth, performing a total of 1,128 ChIP-seq assays across 72 distinct tissue-stages. We combine these histone modification profiles into a unified set of chromatin state annotations, and track their activity across developmental time and space. Through integrative analysis we identify dynamic enhancers, reveal key transcriptional regulators, and characterize the role of chromatin-based repression in developmental gene regulation. We also leverage these data to link enhancers to putative target genes, revealing connections between coding and non-coding sequence variation in disease etiology. Our study provides a compendium of resources for biomedical researchers, and achieves the most comprehensive view of embryonic chromatin states to date.

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An atlas of dynamic chromatin landscapes in mouse fetal development

Nature ◽

10.1038/s41586-020-2093-3 ◽

2020 ◽

Vol 583 (7818) ◽

pp. 744-751 ◽

Cited By ~ 13

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.

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Annotation of Chromatin States in 66 Complete Mouse Epigenomes During Development

10.1101/2020.07.23.218552 ◽

2020 ◽

Author(s):

Arjan van der Velde ◽

Kaili Fan ◽

Junko Tsuji ◽

Jill Moore ◽

Michael Purcaro ◽

...

Keyword(s):

Time Course ◽

Target Genes ◽

Cell Types ◽

Developmental Time ◽

Developmental Trajectory ◽

Phase Iii ◽

Chromatin State ◽

Mammalian Development ◽

Chromatin States ◽

Transcription Start Sites

ABSTRACTThe morphologically and functionally distinct cell types of a multicellular organism are maintained by epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 10.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions throughout the developmental time course. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by Polycomb Repressive Complex proteins and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.

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Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data

BMC Genomics ◽

10.1186/s12864-021-07373-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Henriette Miko ◽

Yunjiang Qiu ◽

Bjoern Gaertner ◽

Maike Sander ◽

Uwe Ohler

Keyword(s):

Time Series ◽

Histone Modifications ◽

Gene Activation ◽

Expectation Maximization Algorithm ◽

Chromatin State ◽

Open Chromatin ◽

Multiple Time ◽

Enhancer Activity ◽

Chromatin States ◽

Multiple Time Points

Abstract Background Co-localized combinations of histone modifications (“chromatin states”) have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points (“chromatin state trajectories”) have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. Results We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex. Conclusions TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.

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Annotation of chromatin states in 66 complete mouse epigenomes during development

Communications Biology ◽

10.1038/s42003-021-01756-4 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Arjan van der Velde ◽

Kaili Fan ◽

Junko Tsuji ◽

Jill E. Moore ◽

Michael J. Purcaro ◽

...

Keyword(s):

Target Genes ◽

Cell Types ◽

Developmental Trajectory ◽

Phase Iii ◽

Chromatin State ◽

Mammalian Development ◽

Chromatin States ◽

Transcription Start Sites ◽

Repressive Mark ◽

Distinct Cell

AbstractThe morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.

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chromstaR: Tracking combinatorial chromatin state dynamics in space and time

10.1101/038612 ◽

2016 ◽

Cited By ~ 11

Author(s):

Aaron Taudt ◽

Minh Anh Nguyen ◽

Matthias Heinig ◽

Frank Johannes ◽

Maria Colomé-Tatché

Keyword(s):

Temporal Dynamics ◽

Cell Types ◽

R Package ◽

Developmental Time ◽

Genomic Region ◽

Chromatin State ◽

Post Translational Modifications ◽

Chromatin States ◽

Genome Wide ◽

Experimental Treatments

AbstractBackgroundPost-translational modifications of histone residue tails are an important component of genome regulation. It is becoming increasingly clear that the combinatorial presence and absence of various modifications define discrete chromatin states which determine the functional properties of a locus. An emerging experimental goal is to track changes in chromatin state maps across different conditions, such as experimental treatments, cell-types or developmental time points.ResultsHere we present chromstaR, an algorithm for the computational inference of combinatorial chromatin state dynamics across an arbitrary number of conditions. ChromstaR uses a multivariate Hidden Markov Model to determine the number of discrete combinatorial chromatin states using multiple ChIP-seq experiments as input and assigns every genomic region to a state based on the presence/absence of each modification in every condition. We demonstrate the advantages of chromstaR in the context of three common experimental data scenarios. First, we study how different histone modifications combine to form combinatorial chromatin states in a single tissue. Second, we infer genome-wide patterns of combinatorial state differences between two cell types or conditions. Finally, we study the dynamics of combinatorial chromatin states during tissue differentiation involving up to six differentiation points. Our findings reveal a striking sparcity in the combinatorial organization and temporal dynamics of chromatin state maps.ConclusionschromstaR is a versatile computational tool that facilitates a deeper biological understanding of chromatin organization and dynamics. The algorithm is implemented as an R-package and freely available from http://bioconductor.org/packages/chromstaR/.

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Chromatin dynamics associated with sexual differentiation in a UV sex determination system

10.1101/2020.10.29.359190 ◽

2020 ◽

Author(s):

Josselin Gueno ◽

Simon Bourdareau ◽

Guillaume Cossard ◽

Olivier Godfroy ◽

Agnieszka Lipinska ◽

...

Keyword(s):

Gene Expression ◽

Sex Determination ◽

Histone Modifications ◽

Sex Chromosomes ◽

Sexual Differentiation ◽

Chromatin State ◽

State Transitions ◽

Male And Female ◽

Chromatin States ◽

Males And Females

SummaryIn many eukaryotes, such as dioicous mosses and many algae, sex is determined by UV sex chromosomes and is expressed during the haploid phase of the life cycle. In these species, the male and female developmental programs are initiated by the presence of the U- or V-specific regions of the sex chromosomes but, as in XY and ZW systems, phenotypic differentiation is largely driven by autosomal sex-biased gene expression. The mechanisms underlying sex-biased transcription in XY, ZW or UV sexual systems currently remain elusive. Here, we set out to understand the extent and nature of epigenomic changes associated with sexual differentiation in the brown alga Ectocarpus, which has a well described UV system. Five histone modifications, H3K4me3, H3K27Ac, H3K9Ac, H3K36me3, H4K20me3, were quantified in near-isogenic male and female lines, leading to the identification of 13 different chromatin states across the Ectocarpus genome that showed different patterns of enrichment at transcribed, silent, housekeeping or narrowly-expressed genes. Chromatin states were strongly correlated with levels of gene expression indicating a relationship between the assayed marks and gene transcription. The relative proportion of each chromatin state across the genome remained stable in males and females, but a subset of genes exhibited different chromatin states in the two sexes. In particular, males and females displayed distinct patterns of histone modifications at sex-biased genes, indicating that chromatin state transitions occur preferentially at genes involved in sex-specific pathways. Finally, our results reveal a unique chromatin landscape of the U and V sex chromosomes compared to autosomes. Taken together, our observations reveal a role for histone modifications in sex determination and sexual differentiation in a UV sexual system, and suggest that the mechanisms of epigenetic regulation of genes on the UV sex chromosomes may differ from those operating on autosomal genes.

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Non-Coding, RNAPII-Dependent Transcription at the Promoters of rRNA Genes Regulates Their Chromatin State in S. cerevisiae

Non-Coding RNA ◽

10.3390/ncrna7030041 ◽

2021 ◽

Vol 7 (3) ◽

pp. 41

Author(s):

Emma Lesage ◽

Jorge Perez-Fernandez ◽

Sophie Queille ◽

Christophe Dez ◽

Olivier Gadal ◽

...

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Tandem Repeats ◽

Chromatin State ◽

Rrna Genes ◽

Rdna Genes ◽

Regulatory Pathways ◽

Chromatin States ◽

Non Coding Rnas ◽

Pervasive Transcription

Pervasive transcription is widespread in eukaryotes, generating large families of non-coding RNAs. Such pervasive transcription is a key player in the regulatory pathways controlling chromatin state and gene expression. Here, we describe long non-coding RNAs generated from the ribosomal RNA gene promoter called UPStream-initiating transcripts (UPS). In yeast, rDNA genes are organized in tandem repeats in at least two different chromatin states, either transcribed and largely depleted of nucleosomes (open) or assembled in regular arrays of nucleosomes (closed). The production of UPS transcripts by RNA Polymerase II from endogenous rDNA genes was initially documented in mutants defective for rRNA production by RNA polymerase I. We show here that UPS are produced in wild-type cells from closed rDNA genes but are hidden within the enormous production of rRNA. UPS levels are increased when rDNA chromatin states are modified at high temperatures or entering/leaving quiescence. We discuss their role in the regulation of rDNA chromatin states and rRNA production.

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Antagonising Chromatin Remodelling Activities in the Regulation of Mammalian Ribosomal Transcription

Genes ◽

10.3390/genes12070961 ◽

2021 ◽

Vol 12 (7) ◽

pp. 961

Author(s):

Kanwal Tariq ◽

Ann-Kristin Östlund Farrants

Keyword(s):

Stress Responses ◽

Ribosomal Gene ◽

Chromatin Remodelling ◽

Chromatin State ◽

Rrna Gene ◽

Open Chromatin ◽

Histone Chaperones ◽

Embryonic Cells ◽

Cell Type ◽

Chromatin States

Ribosomal transcription constitutes the major energy consuming process in cells and is regulated in response to proliferation, differentiation and metabolic conditions by several signalling pathways. These act on the transcription machinery but also on chromatin factors and ncRNA. The many ribosomal gene repeats are organised in a number of different chromatin states; active, poised, pseudosilent and repressed gene repeats. Some of these chromatin states are unique to the 47rRNA gene repeat and do not occur at other locations in the genome, such as the active state organised with the HMG protein UBF whereas other chromatin state are nucleosomal, harbouring both active and inactive histone marks. The number of repeats in a certain state varies on developmental stage and cell type; embryonic cells have more rRNA gene repeats organised in an open chromatin state, which is replaced by heterochromatin during differentiation, establishing different states depending on cell type. The 47S rRNA gene transcription is regulated in different ways depending on stimulus and chromatin state of individual gene repeats. This review will discuss the present knowledge about factors involved, such as chromatin remodelling factors NuRD, NoRC, CSB, B-WICH, histone modifying enzymes and histone chaperones, in altering gene expression and switching chromatin states in proliferation, differentiation, metabolic changes and stress responses.

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Transcription of c-onc genes c-rasKi and c-fms during mouse development

Molecular and Cellular Biology ◽

10.1128/mcb.3.6.1062-1069.1983 ◽

1983 ◽

Vol 3 (6) ◽

pp. 1062-1069

Author(s):

R Müller ◽

D J Slamon ◽

E D Adamson ◽

J M Tremblay ◽

D Müller ◽

...

Keyword(s):

Gene Product ◽

Time Course ◽

Specific Pattern ◽

Yolk Sac ◽

Transport Processes ◽

Mouse Development ◽

Mrna Species ◽

Mouse Tissues ◽

Sarcoma Virus ◽

Significant Expression

We investigated the expression of cellular sequences c-rasKi and c-fms, which are homologous to the oncogenes of Kirsten rat sarcoma virus and the McDonough strain of feline sarcoma virus, during murine development and in a variety of mouse tissues. The c-rasKi gene was found to be transcribed into two mRNA species of approximately 2.0 and 4.4 kilobases, whereas a single c-fms-related transcript of approximately 3.7 kilobases was identified. The c-rasKi gene appeared to be expressed ubiquitously, since similar levels of transcripts were observed in embryos, fetuses, extraembryonal structures, and a variety of postnatal tissues. In contrast, significant expression of c-fms was found to be confined to the placenta and extraembryonal membranes (i.e., combined yolk sac and amnion). The concentration of c-fms transcripts in the placenta increased approximately 15-fold (relative to day-7 to day-9 conceptuses) during development before reaching a plateau at day 14 to 15 of gestation. The time course of cfms expression in the extraembryonal membranes appeared to parallel the stage-specific pattern observed in the placenta. The level of c-fms transcripts in the extraembryonal tissues reached a level which was approximately 20- to 50-fold greater than that in the fetus. These findings suggest that the c-fms gene product may play a role in differentiation of extraembryonal structures or in transport processes occurring in these tissues. Our results indicate that the c-onc genes analyzed in the present study exert essentially different functions during mouse development.

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Identification of polycomb repressive complex 1 and 2 core components in hexaploid bread wheat

BMC Plant Biology ◽

10.1186/s12870-020-02384-6 ◽

2020 ◽

Vol 20 (S1) ◽

Author(s):

Beáta Strejčková ◽

Radim Čegan ◽

Ales Pecinka ◽

Zbyněk Milec ◽

Jan Šafář

Keyword(s):

Bread Wheat ◽

Developmental Stages ◽

Gene Families ◽

Polycomb Group ◽

Transcriptional Analysis ◽

Histone H2a ◽

Polycomb Repressive Complex ◽

Core Components ◽

High Level ◽

Polycomb Repressive Complex 1

Abstract Background Polycomb repressive complexes 1 and 2 play important roles in epigenetic gene regulation by posttranslationally modifying specific histone residues. Polycomb repressive complex 2 is responsible for the trimethylation of lysine 27 on histone H3; Polycomb repressive complex 1 catalyzes the monoubiquitination of histone H2A at lysine 119. Both complexes have been thoroughly studied in Arabidopsis, but the evolution of polycomb group gene families in monocots, particularly those with complex allopolyploid origins, is unknown. Results Here, we present the in silico identification of the Polycomb repressive complex 1 and 2 (PRC2, PRC1) subunits in allohexaploid bread wheat, the reconstruction of their evolutionary history and a transcriptional analysis over a series of 33 developmental stages. We identified four main subunits of PRC2 [E(z), Su(z), FIE and MSI] and three main subunits of PRC1 (Pc, Psc and Sce) and determined their chromosomal locations. We found that most of the genes coding for subunit proteins are present as paralogs in bread wheat. Using bread wheat RNA-seq data from different tissues and developmental stages throughout plant ontogenesis revealed variable transcriptional activity for individual paralogs. Phylogenetic analysis showed a high level of protein conservation among temperate cereals. Conclusions The identification and chromosomal location of the Polycomb repressive complex 1 and 2 core components in bread wheat may enable a deeper understanding of developmental processes, including vernalization, in commonly grown winter wheat.

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