scholarly journals The cis-regulatory codes of response to combined heat and drought stress in Arabidopsis thaliana

2020 ◽  
Author(s):  
Christina B. Azodi ◽  
John P. Lloyd ◽  
Shin-Han Shiu
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factors ◽  
Drought Stress ◽  
Transcriptional Response ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Combined Stress ◽  
Binding Motifs ◽  
Powerful Approach ◽  
The Individual

ABSTRACTPlants respond to their environment by dynamically modulating gene expression. A powerful approach for understanding how these responses are regulated is to integrate information about cis-regulatory elements (CREs) into models called cis-regulatory codes. Transcriptional response to combined stress is typically not the sum of the responses to the individual stresses. However, cis-regulatory codes underlying combined stress response have not been established. Here we modeled transcriptional response to single and combined heat and drought stress in Arabidopsis thaliana. We grouped genes by their pattern of response (independent, antagonistic, synergistic) and trained machine learning models to predict their response using putative CREs (pCREs) as features (median F-measure = 0.64). We then developed a deep learning approach to integrate additional omics information (sequence conservation, chromatin accessibility, histone modification) into our models, improving performance by 6.2%. While pCREs important for predicting independent and antagonistic responses tended to resemble binding motifs of transcription factors associated with heat and/or drought stress, important synergistic pCREs resembled binding motifs of transcription factors not known to be associated with stress. These findings demonstrate how in silico approaches can improve our understanding of the complex codes regulating response to combined stress and help us identify prime targets for future characterization.

scholarly journals The cis-regulatory codes of response to combined heat and drought stress in Arabidopsis thaliana

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Christina B Azodi ◽  
John P Lloyd ◽  
Shin-Han Shiu
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factors ◽  
Drought Stress ◽  
Transcriptional Response ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Combined Stress ◽  
Binding Motifs ◽  
Powerful Approach ◽  
The Individual

Abstract Plants respond to their environment by dynamically modulating gene expression. A powerful approach for understanding how these responses are regulated is to integrate information about cis-regulatory elements (CREs) into models called cis-regulatory codes. Transcriptional response to combined stress is typically not the sum of the responses to the individual stresses. However, cis-regulatory codes underlying combined stress response have not been established. Here we modeled transcriptional response to single and combined heat and drought stress in Arabidopsis thaliana. We grouped genes by their pattern of response (independent, antagonistic and synergistic) and trained machine learning models to predict their response using putative CREs (pCREs) as features (median F-measure = 0.64). We then developed a deep learning approach to integrate additional omics information (sequence conservation, chromatin accessibility and histone modification) into our models, improving performance by 6.2%. While pCREs important for predicting independent and antagonistic responses tended to resemble binding motifs of transcription factors associated with heat and/or drought stress, important synergistic pCREs resembled binding motifs of transcription factors not known to be associated with stress. These findings demonstrate how in silico approaches can improve our understanding of the complex codes regulating response to combined stress and help us identify prime targets for future characterization.

scholarly journals Gene regulation gravitates towards either addition or multiplication when combining the effects of two signals

2020 ◽  
Author(s):  
Eric M. Sanford ◽  
Benjamin L. Emert ◽  
Allison Coté ◽  
Arjun Raj
Keyword(s):  
Transcriptional Response ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Mechanistic Models ◽  
Transcriptional Responses ◽  
Genome Wide ◽  
Putative Transcription Factor ◽  
The Individual ◽  
Transcription Factor Occupancy ◽  
Mcf 7

AbstractSignals often ultimately affect the transcription of genes, and often, two different signals can affect the transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. Mechanistic models can predict a range of combined responses, with the most commonly applied models predicting additive or multiplicative responses, but systematic genome-wide evaluation of these predictions are not available. Here, we performed a comprehensive analysis of the transcriptional response of human MCF-7 cells to two different signals (retinoic acid and TGF-β), applied individually and in combination. We found that the combined responses exhibited a range of behaviors, but clearly favored both additive and multiplicative combined transcriptional responses. We also performed paired chromatin accessibility measurements to measure putative transcription factor occupancy at regulatory elements near these genes. We found that increases in chromatin accessibility were largely additive, meaning that the combined accessibility response was the sum of the accessibility responses to each signal individually. We found some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors.

scholarly journals Non-Coding Genome, Transcription Factors, and Sex Determination

2021 ◽  
pp. 1-13
Author(s):  
Francis Poulat
Keyword(s):  
Transcription Factors ◽  
Sex Determination ◽  
Target Genes ◽  
Regulatory Elements ◽  
Eukaryotic Cells ◽  
Genomic Profiling ◽  
Binding Motifs ◽  
Male And Female ◽  
Genome Transcription ◽  
Control Complex

In vertebrates, gonadal sex determination is the process by which transcription factors drive the choice between the testicular and ovarian identity of undifferentiated somatic progenitors through activation of 2 different transcriptional programs. Studies in animal models suggest that sex determination always involves sex-specific transcription factors that activate or repress sex-specific genes. These transcription factors control their target genes by recognizing their regulatory elements in the non-coding genome and their binding motifs within their DNA sequence. In the last 20 years, the development of genomic approaches that allow identifying all the genomic targets of a transcription factor in eukaryotic cells gave the opportunity to globally understand the function of the nuclear proteins that control complex genetic programs. Here, the major transcription factors involved in male and female vertebrate sex determination and the genomic profiling data of mouse gonads that contributed to deciphering their transcriptional regulation role will be reviewed.

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 Learning immune cell differentiation

2019 ◽  
Author(s):  
Alexandra Maslova ◽  
Ricardo N. Ramirez ◽  
Ke Ma ◽  
Hugo Schmutz ◽  
Chendi Wang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Sequence ◽  
Immune Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Binding Motifs ◽  
Human Dna ◽  
High Concordance ◽  
Cell Type Specific

SUMMARYThe mammalian genome contains several million cis-regulatory elements, whose differential activity marked by open chromatin determines organogenesis and differentiation. This activity is itself embedded in the DNA sequence, decoded by sequence-specific transcription factors. Leveraging a granular ATAC-seq atlas of chromatin activity across 81 immune cell-types we show that a convolutional neural network (“AI-TAC”) can learn to infer cell-type-specific chromatin activity solely from the DNA sequence. AI-TAC does so by rediscovering, with astonishing precision, binding motifs for known regulators, and some unknown ones, mapping them with high concordance to positions validated by ChIP-seq data. AI-TAC also uncovers combinatorial influences, establishing a hierarchy of transcription factors (TFs) and their interactions involved in immunocyte specification, with intriguingly different strategies between lineages. Mouse-trained AI-TAC can parse human DNA, revealing a strikingly similar ranking of influential TFs. Thus, Deep Learning can reveal the regulatory syntax that drives the full differentiative complexity of the immune system.

scholarly journals Locally acting transcription factors regulate p53-dependent cis-regulatory element activity

2020 ◽  
Vol 48 (8) ◽  
pp. 4195-4213 ◽  
Author(s):  
Allison N Catizone ◽  
Gizem Karsli Uzunbas ◽  
Petra Celadova ◽  
Sylvia Kuang ◽  
Daniel Bose ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Sequence Context ◽  
Binding Motifs ◽  
Cycle Arrest ◽  
Damage Repair ◽  
Local Sequence ◽  
Element Activity ◽  
Massively Parallel Reporter Assay

Abstract The master tumor suppressor p53 controls transcription of a wide-ranging gene network involved in apoptosis, cell cycle arrest, DNA damage repair, and senescence. Recent studies revealed pervasive binding of p53 to cis-regulatory elements (CREs), which are non-coding segments of DNA that spatially and temporally control transcription through the combinatorial binding of local transcription factors. Although the role of p53 as a strong trans-activator of gene expression is well known, the co-regulatory factors and local sequences acting at p53-bound CREs are comparatively understudied. We designed and executed a massively parallel reporter assay (MPRA) to investigate the effect of transcription factor binding motifs and local sequence context on p53-bound CRE activity. Our data indicate that p53-bound CREs are both positively and negatively affected by alterations in local sequence context and changes to co-regulatory TF motifs. Our data suggest p53 has the flexibility to cooperate with a variety of transcription factors in order to regulate CRE activity. By utilizing different sets of co-factors across CREs, we hypothesize that global p53 activity is guarded against loss of any one regulatory partner, allowing for dynamic and redundant control of p53-mediated transcription.

scholarly journals Regulatory elements encoded in the first intron are necessary for proper expression of the MADS-box transcription factors AGL6 and AGL13 in Arabidopsis thaliana

2008 ◽  
Vol 319 (2) ◽  
pp. 587 ◽  
Author(s):  
Stephen E. Schauer ◽  
Ramarmurthy Baskar ◽  
Philipp Schlüter ◽  
Jacqueline Gheyselinck ◽  
Arturo Bolaños ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factors ◽  
Regulatory Elements ◽  
Mads Box ◽  
First Intron

scholarly journals Effects of individual and combined heat and drought stress during seed filling on the oxidative metabolism and yield of chickpea (Cicer arietinum) genotypes differing in heat and drought tolerance

2017 ◽  
Vol 68 (9) ◽  
pp. 823 ◽  
Author(s):  
Rashmi Awasthi ◽  
Pooran Gaur ◽  
Neil C. Turner ◽  
Vincent Vadez ◽  
Kadambot H. M. Siddique ◽  
...  
Keyword(s):  
Heat Stress ◽  
Drought Stress ◽  
Seed Yield ◽  
Oxidative Metabolism ◽  
Combined Stress ◽  
Seed Filling ◽  
Stress Treatment ◽  
Drought Tolerant ◽  
The Individual ◽  
Drought And Heat Stress

Drought and heat stress are two major constraints that limit chickpea (Cicer arietinum L.) yield, particularly during seed filling. The present study aimed (i) to assess the individual and combined effects of drought and heat stress on oxidative metabolism during seed filling, and (ii) to determine any genetic variation in oxidative metabolism among genotypes differing in drought and heat tolerance and sensitivity. The plants were raised in outdoor conditions with two different times of sowing, one in November (normal-sown, temperatures <32°C−20°C (day–night) during seed filling), and the other in February (late-sown, temperatures >32°C−20°C (day–night) during seed filling). Plants were regularly irrigated to prevent any water shortage until the water treatments were applied. At both sowing times, the drought treatment was applied during seed filling (at ~75% podding) by withholding water from half of the pots until the relative leaf water content (RLWC) of leaves on the top three branches reached 42–45%, whereas leaves in the fully irrigated control plants were maintained at RLWC 85–90%. Drought-stressed plants were then rewatered and maintained under fully irrigated conditions until maturity. Several biochemical parameters were measured on the leaves and seeds at the end of the stress treatments, and seed yield and aboveground biomass were measured at maturity. Individual and combined stresses damaged membranes, and decreased PSII function and leaf chlorophyll content, more so under the combined stress treatment. The levels of oxidative molecules (malondialdehyde (MDA) and H2O2) markedly increased compared with the control plants in all stress treatments, especially across genotypes in the combined heat + drought stress treatment (increases in leaves: MDA 5.4–8.4-fold and H2O2 5.1–7.1-fold; in seeds: MDA 1.9–3.3-fold and H2O2 3.8–7.9-fold). The enzymatic and non-enzymatic antioxidants related to oxidative metabolism increased under individual stress treatments but decreased in the combined heat + drought stress treatment. Leaves had higher oxidative damage than seeds, and this likely inhibited their photosynthetic efficiency. Yields were reduced more by drought stress than by heat stress, with the lowest yields in the combined heat + drought stress treatment. Heat- and drought-tolerant genotypes suffered less damage and had higher yields than the heat- and drought-sensitive genotypes under the individual and combined stress treatments, suggesting partial cross-tolerance in these genotypes. A drought-tolerant genotype ICC8950 produced more seed yield under the combined heat + drought stress than other genotypes, and this was associated with low oxidative damage in leaves and seeds.

scholarly journals The Maize WRKY Transcription Factor ZmWRKY40 Confers Drought Resistance in Transgenic Arabidopsis

2018 ◽  
Vol 19 (9) ◽  
pp. 2580 ◽  
Author(s):  
Chang-Tao Wang ◽  
Jing-Na Ru ◽  
Yong-Wei Liu ◽  
Jun-Feng Yang ◽  
Meng Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Drought Stress ◽  
Stress Response ◽  
Abiotic Stresses ◽  
Transgenic Arabidopsis ◽  
Regulatory Elements ◽  
Wrky Transcription Factor ◽  
Growth And Yield ◽  
Abiotic Stress Response

Abiotic stresses restrict the growth and yield of crops. Plants have developed a number of regulatory mechanisms to respond to these stresses. WRKY transcription factors (TFs) are plant-specific transcription factors that play essential roles in multiple plant processes, including abiotic stress response. At present, little information regarding drought-related WRKY genes in maize is available. In this study, we identified a WRKY transcription factor gene from maize, named ZmWRKY40. ZmWRKY40 is a member of WRKY group II, localized in the nucleus of mesophyll protoplasts. Several stress-related transcriptional regulatory elements existed in the promoter region of ZmWRKY40. ZmWRKY40 was induced by drought, high salinity, high temperature, and abscisic acid (ABA). ZmWRKY40 could rapidly respond to drought with peak levels (more than 10-fold) at 1 h after treatment. Overexpression of ZmWRKY40 improved drought tolerance in transgenic Arabidopsis by regulating stress-related genes, and the reactive oxygen species (ROS) content in transgenic lines was reduced by enhancing the activities of peroxide dismutase (POD) and catalase (CAT) under drought stress. According to the results, the present study may provide a candidate gene involved in the drought stress response and a theoretical basis to understand the mechanisms of ZmWRKY40 in response to abiotic stresses in maize.

scholarly journals Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lucas T Gray ◽  
Zizhen Yao ◽  
Thuc Nghi Nguyen ◽  
Tae Kyung Kim ◽  
Hongkui Zeng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Adult Mouse ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Mouse Cortex ◽  
Mouse Visual Cortex

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.

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