Chromatin accessibility dynamics reveal novel functional enhancers in <i>C. elegans</i>

Daugherty, Aaron C.; Yeo, Robin; Buenrostro, Jason D.; Greenleaf, William J.; Kundaje, Anshul; Brunet, Anne

doi:10.1101/gr.226233.117

Cited by 150 publications

(188 citation statements)

References 92 publications

(20 reference statements)

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“…These results are in keeping with Drosophila, C. elegans and vertebrates in which a minority of loci show a temporally dynamic chromatin accessibility in embryos (Cusanovich et al, 2018;Daugherty et al, 2017;Hagey et al, 2016;Liu et al, 2018;Preissl et al, 2018;Thomas et al, 2011;Wu et al, 2016). We note however that approximately 50% of the peaks showed at least a 2-fold temporal variation in the pattern of chromatin accessibility, as exemplified for the Matrilin-related gene ( Figure 3B).…”

Section: Temporal Dynamics Of Chromatin Accessibility In Phallusia Masupporting

confidence: 88%

Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.

Madgwick

Magri

Dantec

et al. 2018

Preprint

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Open chromatin regions are highly enriched for cis-regulatory elements in ascidian early embryos.• Ascidian Clusters of Open Regulatory Elements (COREs) are found next to regulatory genes.• The spatio-temporal dynamics of chromatin accessibility and closest-gene expression are correlated.• Regulatory gene expression, the trans-regulatory code, is conserved between distantly-related Ciona and Phallusia ascidians. • Ascidians show pervasive use of "shadow" enhancers • The position of homologous enhancers can be conserved, despite extensive genome divergence. ABSTRACT Ascidian species of the Phallusia and Ciona genera are distantly related, their last common ancestor dating several hundred million years ago. Although their genome sequences have extensively diverged since this radiation, Phallusia and Ciona species share almost identical early morphogenesis and stereotyped cell lineages.Here, we explored the evolution of transcriptional control between P. mammillata and C. robusta. We combined genome-wide mapping of open chromatin regions in both species with a comparative analysis of the regulatory sequences of a test set of 10 pairs of orthologous early regulatory genes with conserved expression patterns. We find that ascidian chromatin accessibility landscapes obey similar rules as in other metazoa. Openchromatin regions are short, highly conserved within each genus and cluster around regulatory genes. The dynamics of chromatin accessibility and closest-gene expression are strongly correlated during early embryogenesis. Open-chromatin regions are highly enriched in cis-regulatory elements: 73% of 49 open chromatin regions around our test genes behaved as either distal enhancers or proximal enhancer/promoters following electroporation in Phallusia eggs.Analysis of this datasets suggests a pervasive use in ascidians of "shadow" enhancers with partially overlapping activities. Cross-species electroporations point to a deep conservation of both the transregulatory logic between these distantly-related ascidians and the cis-regulatory activities of individual enhancers. Finally, we found that the relative order and approximate distance to the transcription start site of open chromatin regions can be conserved between Ciona and Phallusia species despite extensive sequence divergence, a property that can be used to identify orthologous enhancers, whose regulatory activity can partially diverge. of chromatin accessibility landscapes and cis-regulatory logic between these species despite extreme sequence divergence.

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Section: Temporal Dynamics Of Chromatin Accessibility In Phallusia Masupporting

confidence: 88%

Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.

Madgwick

Magri

Dantec

et al. 2018

Preprint

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“…S1). General metrics including peak numbers, size, GC content and genomic distribution were comparable to consensus peaksets reported in similar studies of chromatin accessibility in developmental contexts [19][20][21][22][23] (Supplementary text; Fig. S1).…”

Section: A Reference Accessome For Cardiopharyngeal Developmentsupporting

confidence: 74%

Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

Racioppi

Wiechecki

Christiaen

2019

Preprint

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In embryos, lineage-specific profiles of chromatin accessibility control gene expression by modulating transcription, and thus impact multipotent progenitor states and subsequent fate choices. Subsets of cardiac and pharyngeal/head muscles share a common origin in the cardiopharyngeal mesoderm, but the chromatin landscapes that govern multipotent progenitors’ competence and early fate choices remain largely elusive. Here, we leveraged the simplicity of the chordate model Ciona to profile chromatin accessibility through stereotyped transitions from naive Mesp+ mesoderm to distinct fate-restricted heart and pharyngeal muscle precursors. An FGF-Foxf pathway acts in multipotent progenitors to establish cardiopharyngeal-specific patterns of accessibility, which govern later heart vs. pharyngeal muscle-specific expression profiles, demonstrating extensive spatiotemporal decoupling between early cardiopharyngeal enhancer accessibility and late cell-type-specific activity. Combinations of cis-regulatory elements with distinct chromatin accessibility profiles are required to activate of Ebf and Tbx1/10, two key determinants of cardiopharyngeal fate choices. We propose that this higher order combinatorial logic increases the repertoire of regulatory inputs that control gene expression, through either accessibility and/or activity, thus fostering spatially and temporally accurate fate choices.

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“…After processing the reads as described above, reactivated NSPC libraries were downsampled to 40 million reads. Peak calling for all libraries was performed after ATAC-seq specific quality control steps 85 using MACS (Version 2.1.1) 86 with the FDR threshold 0.05. Peaks were assigned to genes using GREAT (Version 3.0.0, https://great.stanford.edu/public/html) 87 , limiting the peak-calling window to −1 kb/+1 kb around transcription start sites (TSS) for proximal gene assignments, and −25 kb/+10 kb around TSS for distal gene assignments.…”

Section: Methodsmentioning

confidence: 99%

Changing and stable chromatin accessibility supports transcriptional overhaul during neural stem cell activation

Maybury-Lewis

Brown

Yeary

et al. 2020

Preprint

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20Adult neural stem cells are largely quiescent, and require transcriptional reprogramming 21 to reenter the cell cycle and undergo neurogenesis. However, the precise mechanisms 22 that underlie the rapid transcriptional overhaul during NSC activation remain undefined. 23Here, we identify the genome-wide chromatin accessibility differences between primary 24 neural stem and progenitor cells in quiescent and activated states. We show that these 25 distinct cellular states exhibit both shared and unique chromatin profiles, which are both 26 associated with gene regulation. Interestingly, we find that accessible chromatin states 27 specific to quiescent or activated cells are active enhancers bound by pro-neurogenic 28 and quiescence factors, ASCL1 and NFI. In contrast, shared sites are gene promoters 29 harboring constitutively accessible chromatin enriched for particular core promoter 30 elements that are functionally associated with translation and metabolic functions. 31Together, our findings reveal how accessible chromatin states regulate a transcriptional 32 overhaul and drive the switch between quiescence and proliferation in NSC activation. 33 34 46In vivo, the majority of NSCs reside in a state of quiescence 10 . Quiescent NSCs (qNSCs) 47 have exited the cell cycle but can be prompted by intrinsic or extrinsic cues to "activate" 48 and re-enter the cell cycle (we refer to these cells as activated NSCs, or aNSCs). Once 49 activated, aNSCs proliferate and may return to quiescence and self-renew, or 50 differentiate into neurons or glia. Activation of qNSCs is the first critical step in 51 neurogenesis in the adult brain, and is enhanced in response to damage (e.g. stroke) or 52 environmental stimuli such as parabiosis [11][12][13] . Evidence shows that decreased 53 neurogenesis with age occurs due to reduced activation of qNSCs, senescence of the 54 NSC niche, and exhaustion of the qNSC pool [14][15][16][17] . Accumulation of qNSCs has also been 55 observed in a rodent model for neurodevelopmental disorders, suggesting that a careful 56 balance of NSC quiescence and activation is necessary for healthy cognitive function 18 . 57However, the precise mechanisms that regulate this balance and prompt qNSCs to re-58 enter the cell cycle in the healthy mammalian brain are mostly unknown. 59 60 Recent studies reported that quiescent and activated NSCs employ cell type-specific 61 mechanisms to support their functionality, including distinct metabolic states and 62 differences in proteostasis [19][20][21] . Transcriptional profiling of qNSCs and aNSCs revealed 63 both shared and distinct transcriptional signatures in the two cell types, indicating that a 64 transcriptional overhaul occurs at a subset of genes during the process of NSC 65 activation 10,19,22,23 . For example, genes involved in cell proliferation, lipid metabolism, and 66 protein homeostasis were differentially expressed in quiescent and activated NSCs. 67 Similar changes have also been observed using in vitro models of NSC quiescence and 68 activation...

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Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

Cited by 150 publications

References 92 publications

Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.

Evolution of the embryonic cis-regulatory landscapes between divergent Phallusia and Ciona ascidians.

Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

Changing and stable chromatin accessibility supports transcriptional overhaul during neural stem cell activation

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