scholarly journals Accurate reconstruction of dynamic gene expression and growth rate profiles from noisy measurements

2021 ◽  
Author(s):  
Gonzalo Andrés Vidal Peña ◽  
Carlos Isaias Vidal Céspedes ◽  
timothy james rudge
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Regulatory Networks ◽  
Fusion Gene ◽  
Measurement Data ◽  
Expression Rate ◽  
Sense And Respond ◽  
Cell Densities ◽  
Multiple Promoter ◽  
Noisy Measurements

Cells face changing environments to which they sense and respond in complex ways, changing their rates of gene expression and growth. Measuring these dynamics is therefore essential to understanding natural and synthetic regulatory networks that give rise to functional phenotypes. However, reconstruction of gene expression and growth rate profiles from typically noisy measurements of cell populations is difficult due to the effects of noise at low cell densities among other factors. We present here a method for estimation of dynamic gene expression rates and biomass growth rates from noisy measurement data, and show that it is several times more accurate than current approaches. We applied our method to multiple promoter-reporter fusion genes. Gene expression rates of such promoter-reporter fusions are typically used as a proxy for transcription rates. However, using our method we show that fusion gene expression rate dynamics are determined at least by the promoter of interest and the downstream reporter.

scholarly journals Programmed cell death 4 and BCR-ABL fusion gene expression are negatively correlated in chronic myeloid leukemia

2016 ◽  
Vol 12 (4) ◽  
pp. 2976-2981 ◽  
Author(s):  
Xia Zhang ◽  
Riming Liu ◽  
Baohua Huang ◽  
Xiaolu Zhang ◽  
Weijuan Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Chronic Myeloid Leukemia ◽  
Programmed Cell Death ◽  
Myeloid Leukemia ◽  
Fusion Gene ◽  
Programmed Cell Death 4

scholarly journals X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Genetics ◽  
2021 ◽  
Author(s):  
Thomas D Brekke ◽  
Emily C Moore ◽  
Shane C Campbell-Staton ◽  
Colin M Callahan ◽  
Zachary A Cheviron ◽  
...  
Keyword(s):  
Gene Expression ◽  
X Chromosome ◽  
Regulatory Networks ◽  
Mammalian Species ◽  
Strongly Correlated ◽  
Placental Development ◽  
Substitution Lines ◽  
Genome Wide ◽  
Highly Sensitive ◽  
First And Second Generation

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals Integrative Modelling of Gene Expression and Digital Phenotypes to Describe Senescence in Wheat

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 909
Author(s):  
Anyela Valentina Camargo Rodriguez
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Computational Modelling ◽  
Plant Morphology ◽  
Reproductive Organs ◽  
Biological Trait ◽  
Cereal Grain ◽  
Plant Level

Senescence is the final stage of leaf development and is critical for plants’ fitness as nutrient relocation from leaves to reproductive organs takes place. Although senescence is key in nutrient relocation and yield determination in cereal grain production, there is limited understanding of the genetic and molecular mechanisms that control it in major staple crops such as wheat. Senescence is a highly orchestrated continuum of interacting pathways throughout the lifecycle of a plant. Levels of gene expression, morphogenesis, and phenotypic development all play key roles. Yet, most studies focus on a short window immediately after anthesis. This approach clearly leaves out key components controlling the activation, development, and modulation of the senescence pathway before anthesis, as well as during the later developmental stages, during which grain development continues. Here, a computational multiscale modelling approach integrates multi-omics developmental data to attempt to simulate senescence at the molecular and plant level. To recreate the senescence process in wheat, core principles were borrowed from Arabidopsis Thaliana, a more widely researched plant model. The resulted model describes temporal gene regulatory networks and their effect on plant morphology leading to senescence. Digital phenotypes generated from images using a phenomics platform were used to capture the dynamics of plant development. This work provides the basis for the application of computational modelling to advance understanding of the complex biological trait senescence. This supports the development of a predictive framework enabling its prediction in changing or extreme environmental conditions, with a view to targeted selection for optimal lifecycle duration for improving resilience to climate change.

scholarly journals Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 350
Author(s):  
Julianty Frost ◽  
Mark Frost ◽  
Michael Batie ◽  
Hao Jiang ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Regulator ◽  
Hydroxylase Activity ◽  
Control Of Gene Expression ◽  
Prolyl Hydroxylases ◽  
Chromatin Organisation ◽  
Sense And Respond ◽  
Almost All ◽  
And Function

Hypoxia—reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.

scholarly journals GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mika J. Välimäki ◽  
Robert S. Leigh ◽  
Sini M. Kinnunen ◽  
Alexander R. March ◽  
Ana Hernández de Sande ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Reporter Gene ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Decisions ◽  
Dual Reporter ◽  
Gene Regulatory ◽  
Reporter Gene Assays

AbstractBackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.

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