scholarly journals Genome-wide measurement of spatial expression in patterning mutants of Drosophila melanogaster

2016 ◽  
Author(s):  
Peter A. Combs ◽  
Michael B. Eisen
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Cell Fate ◽  
Regulation Of Transcription ◽  
Regulation Of Expression ◽  
Combinatorial Regulation ◽  
Over Expression ◽  
Spatial Positioning ◽  
Pattern Specification

AbstractGenome sequencing has become commonplace, but the understanding of how those genomes ultimately specify cell fate during development is still elusive. Extrapolating insights from deep investigation of a handful of developmentally important Drosophila genes to understanding the regulation of all genes is a major challenge. The developing embryo provides a unique opportunity to study the role of gene expression in pattern specification; the precise and consistent spatial positioning of key transcription factors essentially provides separate transcriptional-readout experiments at a critical point in development.We cryosectioned and sequenced mRNA from single Drosophila melanogaster embryos at the blastoderm stage to screen for spatially-varying regulation of transcription. Expanding on our previous screening of wild type embryos, here we present data from dosage mutants for key maternally provided regulators, including depletion of zelda and hunchback and both over-expression and depletion of bicoid. These data recapitulate all of the expected patterning changes driven by these regulators; for instance, we show spatially-confined up-regulation of expression in the bicoid over-expression condition, and down-regulation of those genes in the bicoid knock-down case, consistent with bicoid’s known function as an anterior-localized activator.Our data highlight the role of combinatorial regulation of patterning gene expression. When comparing changes in multiple conditions, genes responsive to one mutation tend to respond to other mutations in a similar fashion. Furthermore, genes that respond differently to these mutations tend to have more complex patterns of TF binding.

scholarly journals Regulation of Expression and Latency in BLV and HTLV

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1079
Author(s):  
Aneta Pluta ◽  
Juan P. Jaworski ◽  
Renée N. Douville
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Spastic Paraparesis ◽  
Viral Gene ◽  
Regulation Of Transcription ◽  
Main Role ◽  
Regulation Of Expression ◽  
Incurable Cancer

Human T-lymphotrophic virus type 1 (HTLV-1) and Bovine leukemia virus (BLV) belong to the Deltaretrovirus genus. HTLV-1 is the etiologic agent of the highly aggressive and currently incurable cancer adult T-cell leukemia (ATL) and a neurological disease HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). BLV causes neoplastic proliferation of B cells in cattle: enzootic bovine leucosis (EBL). Despite the severity of these conditions, infection by HTLV-1 and BLV appear in most cases clinically asymptomatic. These viruses can undergo latency in their hosts. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infection, as well as for pathogenesis in vivo. In this review, we will present the mechanisms that control proviral activation and retroviral latency in deltaretroviruses, in comparison with other exogenous retroviruses. The 5′ long terminal repeats (5′-LTRs) play a main role in controlling viral gene expression. While the regulation of transcription initiation is a major mechanism of silencing, we discuss topics that include (i) the epigenetic control of the provirus, (ii) the cis-elements present in the LTR, (iii) enhancers with cell-type specific regulatory functions, (iv) the role of virally-encoded transactivator proteins, (v) the role of repressors in transcription and silencing, (vi) the effect of hormonal signaling, (vii) implications of LTR variability on transcription and latency, and (viii) the regulatory role of non-coding RNAs. Finally, we discuss how a better understanding of these mechanisms may allow for the development of more effective treatments against Deltaretroviruses.

193 Single Cell RNA-sequencing Reveals a Role of Lipid Metabolism in Muscle Satellite Cells

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 104-105
Author(s):  
Shihuan Kuang ◽  
Feng Yue ◽  
Stephanie Oprescu
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Cell Fate ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Lipid Droplets ◽  
Self Renewal ◽  
Droplet Dynamics ◽  
Single Cell Rna Sequencing

Abstract Single Cell RNA-sequencing (scRNA-seq) is a powerful technique to deconvolute gene expression of various subset of cells intermingled within a complex tissue, such as the skeletal muscle. We first used scRNA-seq to understand dynamics of cell populations and their gene expression during muscle regeneration in murine limb muscles. This leads to the identification of a subset of satellite cells (the resident stem cells of skeletal muscles) with immune gene signatures in regenerating muscles. Next, we used scRNA-seq to examine gene expression dynamics of satellite cells at various status: quiescence, activation, proliferation, differentiation and self-renewal. This analysis uncovers stage-dependent changes in expression of genes related to lipid metabolism. Further analyses lead to the discovery of previously unappreciated dynamics of lipid droplets in satellite cells; and demonstrate that the abundance of the lipid droplets in newly divided satellite daughter cells is linked to cell fate segregation into differentiation versus self-renewal. Perturbation of lipid droplet dynamics through blocking lipolysis disrupts cell fate homeostasis and impairs muscle regeneration. Finally, we show that lipid metabolism regulates the function of satellite cells through two mechanisms. On one hand, lipid metabolism functions as an energy source through fatty acid oxidation (FAO), and blockage of FAO reduces energy production that is critical for satellite cell function. On the other hand, lipid metabolism generates bioactive molecules that influence signaling transduction and gene expression. In this scenario, lipid metabolism and FAO regulate the intracellular levels of acetyl-coA and selective acetylation of PAX7, a pivotal transcriptional factor underlying function of satellite cells. These results together reveal for the first time a critical role of lipid metabolism and lipid droplet dynamics in muscle satellite cell fate determination and regenerative function; and underscore a potential role of dietary fatty acids in satellite cell-dependent muscle development, growth and regeneration.

The Role of Nuclear Stiffness and Resilience in Mechanotransduction

2010 ◽  
Author(s):  
Kris Noel Dahl ◽  
Elizabeth A. Booth-Gauthier ◽  
Alexandre J. S. Ribeiro ◽  
Zhixia Zhong
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Live Cell Imaging ◽  
Volume Fraction ◽  
Direct Role ◽  
Intact Cells ◽  
Large Volume Fraction ◽  
Nuclear Mechanics ◽  
Model Cell

Mechanical force is found to be increasingly important during development and for proper homeostatic maintenance of cells and tissues. The nucleus occupies a large volume fraction of the cell and is interconnected with the cytoskeleton. Here, to determine the direct role of the nucleus itself in converting forces to changes in gene expression, also known as, mechanotransduction, we examine changes in nuclear mechanics and gene reorganization associated with cell fate and with extracellular force. We measure mechanics of nuclei in many model cell systems using micropipette aspiration to show changes in nuclear mechanics. In intact cells we characterize the rheological changes induced in the genome organization with live cell imaging and particle tracking, and we suggest how these changes relate to gene expression.

scholarly journals Distinct molecular etiologies of male and female hepatocellular carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Heini M. Natri ◽  
Melissa A. Wilson ◽  
Kenneth H. Buetow
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Sex Differences ◽  
Differential Expression ◽  
Differential Expression Analysis ◽  
Regulation Of Transcription ◽  
Male And Female ◽  
Differential Effects ◽  
Pathway Enrichment

Abstract Background Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Methods Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. Results By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Conclusions Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.

scholarly journals Epigenetic Regulation of Myogenesis: Focus on the Histone Variants

2021 ◽  
Vol 22 (23) ◽  
pp. 12727
Author(s):  
Joana Esteves de Lima ◽  
Frédéric Relaix
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Epigenetic Regulation ◽  
Muscle Development ◽  
Regulation Of Gene Expression ◽  
Histone Variants ◽  
Myoblast Differentiation ◽  
Post Translational Modifications ◽  
Differentiation Status

Skeletal muscle development and regeneration rely on the successive activation of specific transcription factors that engage cellular fate, promote commitment, and drive differentiation. Emerging evidence demonstrates that epigenetic regulation of gene expression is crucial for the maintenance of the cell differentiation status upon division and, therefore, to preserve a specific cellular identity. This depends in part on the regulation of chromatin structure and its level of condensation. Chromatin architecture undergoes remodeling through changes in nucleosome composition, such as alterations in histone post-translational modifications or exchange in the type of histone variants. The mechanisms that link histone post-translational modifications and transcriptional regulation have been extensively evaluated in the context of cell fate and differentiation, whereas histone variants have attracted less attention in the field. In this review, we discuss the studies that have provided insights into the role of histone variants in the regulation of myogenic gene expression, myoblast differentiation, and maintenance of muscle cell identity.

scholarly journals Regulation of effector gene expression as concerted waves in Leptosphaeria maculans: a two-players game

2021 ◽  
Author(s):  
Colin Clairet ◽  
Elise J Gay ◽  
Antoine Porquier ◽  
Françoise Blaise ◽  
Claire-Line Marais ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oilseed Rape ◽  
Leptosphaeria Maculans ◽  
Pathogenic Fungi ◽  
Plant Pathogenic Fungi ◽  
Host Immune System ◽  
Regulation Of Expression ◽  
Effector Gene ◽  
Effector Genes

During infection, plant pathogenic fungi secrete a set of molecules collectively known as effectors, involved in overcoming the host immune system and in disease establishment. Effector genes are concertedly expressed as waves all along plant pathogenic fungi lifecycle. However, little is known about how coordinated expression of effector genes is regulated. Since many effector genes are located in repeat-rich regions, the role of chromatin remodeling in the regulation of effector expression was recently investigated. In Leptosphaeria maculans, causing stem canker of oilseed rape, we established that the repressive histone modification H3K9me3 (trimethylation of Lysine 9 of Histone H3), deposited by the histone methyltransferase KMT1, was involved in the regulation of expression of genes highly expressed during infection, including effectors. Nevertheless, inactivation of KMT1 did not induce expression of these genes at the same level as observed during infection of oilseed rape, suggesting that a second regulator, such as a transcription factor (TF), might be involved. Pf2, a TF belonging to the Zn2Cys6 fungal specific TF family, was described in several Dothideomycete species as essential for pathogenicity and effector gene expression. We identified the orthologue of Pf2 in L. maculans, LmPf2, and investigated the role of LmPf2 together with KMT1, by inactivating and over-expressing LmPf2 in a wild type (WT) strain and a ∆kmt1 mutant. Functional analyses of the corresponding transformants highlighted an essential role of LmPf2 in the establishment of pathogenesis. Transcriptomic analyses during axenic growth showed that LmPf2 is involved in the control of effector gene expression. We observed an enhanced effect of the over-expression of LmPf2 on effector gene expression in a ∆kmt1 background, suggesting an antagonist role between KMT1 and LmPf2.

scholarly journals Distinct molecular etiologies of male and female hepatocellular carcinoma

2019 ◽  
Author(s):  
Heini M Natri ◽  
Melissa A Wilson ◽  
Kenneth H Buetow
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Sex Differences ◽  
Differential Expression ◽  
Differential Expression Analysis ◽  
Regulation Of Transcription ◽  
Male And Female ◽  
Differential Effects ◽  
Pathway Enrichment

Abstract Background: Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Methods: Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. Results: By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, 305 PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Conclusions: Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.

scholarly journals Supra-physiological levels of Gibberellins/DELLAs alter the patterning, morphology and abundance of root hairs in root tips of A. thaliana seedlings

2021 ◽  
Author(s):  
Iva McCarthy-Suarez
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Epidermal Cell ◽  
Root Hair ◽  
Root Hairs ◽  
Root Tip ◽  
Spatial Patterning ◽  
Root Tips ◽  
Root Epidermis

In spite of the known role of gibberellins (GAs), and of their antagonistic proteins, the DELLAs, in leaf hair production, no investigations, however, have assessed their hypothetical function in the production of root hairs. To this aim, the effects of supra-physiological levels of GAs/DELLAs on the spatial patterning of gene expression of the root hair (CPC) and root non-hair (GL2, EGL3 and WER) epidermal cell fate markers, as well as on the distribution, morphology and abundance of root hairs, were studied in root tips of 5-day-old A. thaliana seedlings. Results showed that excessive levels of GAs/DELLAs impaired the spatial patterning of gene expression of the root hair/non-hair epidermal cell fate markers, as well as the arrangement, shape and frequency of root hairs, giving rise to ectopic hairs and ectopic non-hairs, two-haired cells, two-tipped hairs, branched hairs, longer and denser hairs near the root tip under excessive DELLAs, and shorter and scarcer hairs near the root tip under excessive GAs. However, when the gai-1 (GA-insensitive-1) DELLA mutant protein was specifically over-expressed at the root epidermis, no changes in the patterning or abundance of root hairs occurred. Thus, these results suggest that, in seedlings of A. thaliana, the GAs/DELLAs might have a role in regulating the patterning, morphology and abundance of root hairs by acting from the sub-epidermal tissues of the root.

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