scholarly journals Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luca Livraghi ◽  
Joseph J Hanly ◽  
Steven M Van Bellghem ◽  
Gabriela Montejo-Kovacevich ◽  
Eva SM van der Heijden ◽  
...  
Keyword(s):  
Transposable Element ◽  
Structural Variation ◽  
Chromatin Accessibility ◽  
Colour Pattern ◽  
Phenotypic Switch ◽  
Regulatory Regions ◽  
Cell Identity ◽  
Wing Colour ◽  
Pattern Diversity ◽  
Scale Types

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.

scholarly journals Perfect mimicry between Heliconius butterflies is constrained by genetics and development

2020 ◽  
Vol 287 (1931) ◽  
pp. 20201267
Author(s):  
Steven M. Van Belleghem ◽  
Paola A. Alicea Roman ◽  
Heriberto Carbia Gutierrez ◽  
Brian A. Counterman ◽  
Riccardo Papa
Keyword(s):  
Morphological Evolution ◽  
Relative Size ◽  
Colour Pattern ◽  
Butterfly Species ◽  
Closely Related Species ◽  
Wing Colour ◽  
Pattern Diversity ◽  
Heliconius Melpomene ◽  
Gene Regulatory ◽  
Phenotypic Convergence

Müllerian mimicry strongly exemplifies the power of natural selection. However, the exact measure of such adaptive phenotypic convergence and the possible causes of its imperfection often remain unidentified. Here, we first quantify wing colour pattern differences in the forewing region of 14 co-mimetic colour pattern morphs of the butterfly species Heliconius erato and Heliconius melpomene and measure the extent to which mimicking colour pattern morphs are not perfectly identical. Next, using gene-editing CRISPR/Cas9 KO experiments of the gene WntA , which has been mapped to colour pattern diversity in these butterflies, we explore the exact areas of the wings in which WntA affects colour pattern formation differently in H. erato and H. melpomene. We find that, while the relative size of the forewing pattern is generally nearly identical between co-mimics, the CRISPR/Cas9 KO results highlight divergent boundaries in the wing that prevent the co-mimics from achieving perfect mimicry. We suggest that this mismatch may be explained by divergence in the gene regulatory network that defines wing colour patterning in both species, thus constraining morphological evolution even between closely related species.

scholarly journals High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Pierce ◽  
Jeffrey M. Granja ◽  
William J. Greenleaf
Keyword(s):  
Transcription Factor ◽  
Single Cell ◽  
Cancer Cells ◽  
High Throughput ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Chromatin Accessibility ◽  
Regulatory Regions ◽  
Factor Binding ◽  
Genome Wide

AbstractChromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

scholarly journals GATA2 regulates mast cell identity and responsiveness to antigenic stimulation by promoting chromatin remodeling at super-enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yapeng Li ◽  
Junfeng Gao ◽  
Mohammad Kamran ◽  
Laura Harmacek ◽  
Thomas Danhorn ◽  
...  
Keyword(s):  
Mast Cell ◽  
Binding Sites ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Chromatin Accessibility ◽  
Antigenic Stimulation ◽  
Parasitic Infections ◽  
Cell Identity ◽  
Super Enhancer ◽  
Determining Factors

AbstractMast cells are critical effectors of allergic inflammation and protection against parasitic infections. We previously demonstrated that transcription factors GATA2 and MITF are the mast cell lineage-determining factors. However, it is unclear whether these lineage-determining factors regulate chromatin accessibility at mast cell enhancer regions. In this study, we demonstrate that GATA2 promotes chromatin accessibility at the super-enhancers of mast cell identity genes and primes both typical and super-enhancers at genes that respond to antigenic stimulation. We find that the number and densities of GATA2- but not MITF-bound sites at the super-enhancers are several folds higher than that at the typical enhancers. Our studies reveal that GATA2 promotes robust gene transcription to maintain mast cell identity and respond to antigenic stimulation by binding to super-enhancer regions with dense GATA2 binding sites available at key mast cell genes.

scholarly journals The Roles of Chromatin Accessibility in Regulating the Candida albicans White-Opaque Phenotypic Switch

2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday
Keyword(s):  
Candida Albicans ◽  
Cell Fate ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Phenotypic Switching ◽  
Phenotypic Switch ◽  
Chromatin Remodelers ◽  
Environmental Signals ◽  
Cell Fate Decisions ◽  
Simple Model System

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.

scholarly journals Super Enhancer Profiles Identify Key Cell Identity Genes During Differentiation From Embryonic Stem Cells to Trophoblast Stem Cells Super Enhencers in Trophoblast Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongpu Jia ◽  
Yu Gao ◽  
Song Guo ◽  
Si Li ◽  
Liangji Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryo Implantation ◽  
Control Cell ◽  
Embryonic Stem ◽  
Growth Factor Receptor ◽  
Chromatin Accessibility ◽  
Integrated Analysis ◽  
Cell Identity ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

Trophoblast stem cells (TSCs) are derived from blastocysts and the extra-embryonic ectoderm (ExE) of post-implantation embryos and play a significant role in fetal development, but the roles that TSCs play in the earlier status of fetal diseases need further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development and may participate in TSC differentiation. We identified key cell identity genes regulated by TSC-SEs via integrated analysis of H3K27ac and H3K4me1 chromatin immunoprecipitation sequencing (ChIP-seq), RNA-sequencing (RNA-seq) and ATAC-sequencing (ATAC-seq) data. The identified key TSC identity genes regulated by SEs, such as epidermal growth factor receptor (EGFR), integrin β5 (ITGB5) and Paxillin (Pxn), were significantly upregulated during TSC differentiation, and the transcription network mediated by TSC-SEs enriched in terms like focal adhesion and actin cytoskeleton regulation related to differentiation of TSCs. Additionally, the increased chromatin accessibility of the key cell identity genes verified by ATAC-seq further demonstrated the regulatory effect of TSC-SEs on TSC lineage commitment. Our results illustrated the significant roles of the TSC-SE-regulated network in TSC differentiation, and identified key TSC identity genes EGFR, ITGB5 and Pxn, providing novel insight into TSC differentiation and lays the foundation for future studies on embryo implantation and related diseases.

TRlnc: a comprehensive database for human transcriptional regulatory information of lncRNAs

2020 ◽  
Author(s):  
Yanyu Li ◽  
Xuecang Li ◽  
Yongsan Yang ◽  
Meng Li ◽  
Fengcui Qian ◽  
...  
Keyword(s):  
Chromatin Accessibility ◽  
Process Data ◽  
Regulatory Regions ◽  
Comprehensive Database ◽  
Super Enhancer ◽  
Annotation Information ◽  
Transcriptional Regulatory ◽  
Regulatory Information ◽  
Risk Snps ◽  
Transcriptional Regulatory Mechanisms

Abstract Long noncoding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and biological functions. With the increasing study of human diseases and biological processes, information in human H3K27ac ChIP-seq, ATAC-seq and DNase-seq datasets is accumulating rapidly, resulting in an urgent need to collect and process data to identify transcriptional regulatory regions of lncRNAs. We therefore developed a comprehensive database for human regulatory information of lncRNAs (TRlnc, http://bio.licpathway.net/TRlnc), which aimed to collect available resources of transcriptional regulatory regions of lncRNAs and to annotate and illustrate their potential roles in the regulation of lncRNAs in a cell type-specific manner. The current version of TRlnc contains 8 683 028 typical enhancers/super-enhancers and 32 348 244 chromatin accessibility regions associated with 91 906 human lncRNAs. These regions are identified from over 900 human H3K27ac ChIP-seq, ATAC-seq and DNase-seq samples. Furthermore, TRlnc provides the detailed genetic and epigenetic annotation information within transcriptional regulatory regions (promoter, enhancer/super-enhancer and chromatin accessibility regions) of lncRNAs, including common SNPs, risk SNPs, eQTLs, linkage disequilibrium SNPs, transcription factors, methylation sites, histone modifications and 3D chromatin interactions. It is anticipated that the use of TRlnc will help users to gain in-depth and useful insights into the transcriptional regulatory mechanisms of lncRNAs.

A description of Echo perornata spec. nov. from Xizang (Tibet), China (Odonata: Calopterygidae)

Zootaxa ◽  
2012 ◽  
Vol 3218 (1) ◽  
pp. 40
Author(s):  
XIN YU ◽  
MATTI HÄMÄLÄINEN
Keyword(s):  
New Species ◽  
Colour Pattern ◽  
Autonomous Region ◽  
Wing Colour ◽  
First Time

Echo perornata Yu & Hämäläinen, spec. nov. (holotype ♂, China, Xizang Autonomous Region [Tibet], Motuo [Medog], alt. 850m, 1 vii 1983) is described and illustrated for both sexes. The new species has a pale pterostigma shaped quite similarly to that of Echo margarita Selys, 1853, but it differs in wing colour pattern and structure of the penis. E. margarita is recorded from China (Yunnan, Ruili) for the first time.

scholarly journals Heritable variation in colour patterns mediating individual recognition

2017 ◽  
Vol 4 (2) ◽  
pp. 161008 ◽  
Author(s):  
Michael J. Sheehan ◽  
Juanita Choo ◽  
Elizabeth A. Tibbetts
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Phenotypic Diversity ◽  
Individual Recognition ◽  
Genetic Correlations ◽  
Colour Pattern ◽  
Heritable Variation ◽  
Pattern Diversity ◽  
Selection For ◽  
Colour Patterns

Understanding the developmental and evolutionary processes that generate and maintain variation in natural populations remains a major challenge for modern biology. Populations of Polistes fuscatus paper wasps have highly variable colour patterns that mediate individual recognition. Previous experimental and comparative studies have provided evidence that colour pattern diversity is the result of selection for individuals to advertise their identity. Distinctive identity-signalling phenotypes facilitate recognition, which reduces aggression between familiar individuals in P. fuscatus wasps. Selection for identity signals may increase phenotypic diversity via two distinct modes of selection that have different effects on genetic diversity. Directional selection for increased plasticity would greatly increase phenotypic diversity but decrease genetic diversity at associated loci. Alternatively, heritable identity signals under balancing selection would maintain genetic diversity at associated loci. Here, we assess whether there is heritable variation underlying colour pattern diversity used for facial recognition in a wild population of P. fuscatus wasps. We find that colour patterns are heritable and not Mendelian, suggesting that multiple loci are involved. Additionally, patterns of genetic correlations among traits indicated that many of the loci underlying colour pattern variation are unlinked and independently segregating. Our results support a model where the benefits of being recognizable maintain genetic variation at multiple unlinked loci that code for phenotypic diversity used for recognition.

scholarly journals Chemical signals act as the main reproductive barrier between sister and mimeticHeliconiusbutterflies

2019 ◽  
Author(s):  
M.F. González-Rojas ◽  
K. Darragh ◽  
J Robles ◽  
M. Linares ◽  
S Schulz ◽  
...  
Keyword(s):  
Reproductive Isolation ◽  
Related Species ◽  
Mate Recognition ◽  
Geographic Region ◽  
Reproductive Barrier ◽  
Colour Pattern ◽  
Chemical Profile ◽  
Closely Related Species ◽  
Wing Colour ◽  
Behavioural Experiments

ABSTRACTColour pattern has been long recognised as the trait that drives mate recognition betweenHeliconiusspecies that are phylogenetically close. However, when this cue is compromised such as in cases of mimetic, sympatric and closely related species, alternative mating signals must evolve to ensure reproductive isolation and species integrity. The closely related speciesHeliconius melpomene malletiandH. timareta florencia, occur in the same geographic region and despite being co-mimics they display strong reproductive isolation. In order to test which cues differ between species, and therefore potentially contribute to reproductive isolation, we quantified differences in wing phenotype and male chemical profile. As expected, wing colour pattern was indistinguishable between the two species while the chemical profile of their male sex pheromones showed marked differences. We then conducted behavioural experiments to study the importance of these signals in mate recognition by females. In agreement with our previous results, we found that pheromones and not wing colour pattern drive the preference of females by conspecific males. In addition, experiments with hybrid males and females suggested an important genetic component for both pheromone production and preference. Altogether, these results suggest that pheromones are the major reproductive barrier opposing gene flow between these two sister and co-mimic species.

scholarly journals Super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers

2018 ◽  
Author(s):  
Aziz Khan ◽  
Anthony Mathelier ◽  
Xuegong Zhang
Keyword(s):  
Control Cell ◽  
Cell Types ◽  
Small Subset ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Regulatory Regions ◽  
Cell Identity ◽  
Transcription Start Sites ◽  
Numerous Cell ◽  
Cell Type Specific

AbstractBackgroundSuper-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants. Specifically, super-enhancers are clusters of enhancers defined based on the binding occupancy of master transcription factors (TFs), chromatin regulators, or chromatin marks, while stretch enhancers are large chromatin-defined regulatory regions of at least 3,000 base pairs. Several studies have characterized these regulatory regions in numerous cell types and tissues to decipher their functional importance. However, the differences and similarities between these regulatory regions have not been fully assessed.ResultsWe integrated genomic, epigenomic, and transcriptomic data from ten human cell types to perform a comparative analysis of super and stretch enhancers with respect to their chromatin profiles, cell-type-specificity, and ability to control gene expression. We found that stretch enhancers are more abundant, more distal to transcription start sites, cover twice as much the genome and are significantly less conserved than super-enhancers. In contrast, super-enhancers are significantly more enriched for active chromatin marks and cohesin complex and transcriptionally active than stretch enhancers. Importantly, a vast majority of superenhancers (85%) overlap with only a small subset of stretch enhancers (13%), which are enriched for cell-type-specific biological functions, and control cell identity genes.ConclusionsThese results suggest that super-enhancers are transcriptionally more active and cell-type-specific than stretch enhancers, and importantly, most of the stretch enhancers that are distinct from superenhancers do not show an association with cell identity genes, are less active, and more likely to be poised enhancers.

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