scholarly journals In Silico Prediction of Transcription Factor Collaborations Underlying Phenotypic Sexual Dimorphism in Zebrafish (Danio rerio)

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 873
Author(s):  
Shahrbanou Hosseini ◽  
Armin Otto Schmitt ◽  
Jens Tetens ◽  
Bertram Brenig ◽  
Henner Simianer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Sexual Dimorphism ◽  
Sex Determination ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Colour Pattern ◽  
Promoter Regions ◽  
Dimorphic Gene Expression

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.

scholarly journals Phosphorylation of Serine114 of the transcription factor ABSCISIC ACID INSENSITIVE 4 is essential for activity

2020 ◽  
Author(s):  
Nadav Eisner ◽  
Tzofia Maymon ◽  
Ester Cancho Sanchez ◽  
Dana Bar-Zvi ◽  
Sagie Brodsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Stress Responses ◽  
Lateral Root ◽  
Map Kinases ◽  
Regulation Of Gene Expression ◽  
List Type ◽  
Lateral Root Development ◽  
Aba Insensitive

AbstractThe transcription factor ABA-INSENSITIVE(ABI)4 has diverse roles in regulating plant growth, including inhibiting germination and reserve mobilization in response to ABA and high salinity, inhibiting seedling growth in response to high sugars, inhibiting lateral root growth, and repressing light-induced gene expression. ABI4 activity is regulated at multiple levels, including gene expression, protein stability, and activation by phosphorylation. Although ABI4 can be phosphorylated at multiple residues by MAPKs, we found that S114 is the preferred site of MPK3. To examine the possible biological role of S114 phosphorylation, we transformed abi4-1 mutant plants with ABI4pro::ABI4 constructs encoding wild type (114S), phosphorylation-null (S114A) or phosphomimetic (S114E) forms of ABI4. Phosphorylation of S114 is necessary for the response to ABA, glucose, salt stress, and lateral root development, where the abi4 phenotype could be complemented by expressing ABI4(114S) or ABI4(S114E) but not ABI4(S114A). Comparison of root transcriptomes in ABA-treated roots of abi4-1 mutant plants transformed with constructs encoding the different phosphorylation-forms of S114 of ABI4 revealed that 85% of the ABI4-regulated genes whose expression pattern could be restored by expressing ABI4(114S) are down-regulated by ABI4. Over half of the ABI4-modulated genes were independent of the phosphorylation state of ABI4; these are enriched for stress responses. Phosphorylation of S114 was required for regulation of 35% of repressed genes, but only 17% of induced genes. The genes whose repression requires the phosphorylation of S114 are mainly involved in embryo and seedling development, growth and differentiation, and regulation of gene expression.HighlightsTranscription factor ABI4 is a substrate of MAP kinases.MPK3 preferentially phosphorylates Serine 114 of ABI4.Phosphorylated Serine 114 of ABI4 is required for the complementation of abi4 mutants.Phosphorylated ABI4 acts primarily as a repressor.

scholarly journals Transvection regulates the sex-biased expression of a fly X-linked gene

Science ◽  
2021 ◽  
Vol 371 (6527) ◽  
pp. 396-400 ◽  
Author(s):  
Charalampos Chrysovalantis Galouzis ◽  
Benjamin Prud’homme
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Sex Determination ◽  
Expression Pattern ◽  
X Chromosome ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Regulatory Interaction ◽  
Linked Gene ◽  
Homologous Chromosomes

Sexual dimorphism in animals results from sex-biased gene expression patterns. These patterns are controlled by genetic sex determination hierarchies that establish the sex of an individual. Here we show that the male-biased wing expression pattern of the Drosophila biarmipes gene yellow, located on the X chromosome, is independent of the fly sex determination hierarchy. Instead, we find that a regulatory interaction between yellow alleles on homologous chromosomes (a process known as transvection) silences the activity of a yellow enhancer functioning in the wing. Therefore, this enhancer can be active in males (XY) but not in females (XX). This transvection-dependent enhancer silencing requires the yellow intron and the chromatin architecture protein Mod(mdg4). Our results suggest that transvection can contribute more generally to the sex-biased expression of X-linked genes.

scholarly journals Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahsa Ghorbaninejad ◽  
Maliheh Khademi-Shirvan ◽  
Samaneh Hosseini ◽  
Mohamadreza Baghaban Eslaminejad
Keyword(s):  
Gene Expression ◽  
Osteogenic Differentiation ◽  
Enzyme Inhibitors ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Regulate Gene Expression ◽  
Cell Based Therapy

Abstract Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is a critical step in the treatment of bone defects and skeletal disorders, which present challenges for cell-based therapy and regenerative medicine. Thus, it is necessary to understand the regulatory agents involved in osteogenesis. Epigenetic mechanisms are considered to be the primary mediators that regulate gene expression during MSC differentiation. In recent years, epigenetic enzyme inhibitors have been used as epidrugs in cancer therapy. A number of studies mentioned the role of epigenetic inhibitors in the regulation of gene expression patterns related to osteogenic differentiation. This review attempts to provide an overview of the key regulatory agents of osteogenesis: transcription factors, signaling pathways, and, especially, epigenetic mechanisms. In addition, we propose to introduce epigenetic enzyme inhibitors (epidrugs) and their applications as future therapeutic approaches for bone defect regeneration.

ChIP-on-Chip Analysis Identified HLXB9 as a Transcription Factor In Hematopoietic Cells and Alters the Expression of Genes Involved In Cell-Adhesion

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2486-2486
Author(s):  
Sarah Wildenhain ◽  
Christian Ruckert ◽  
Svenja Daschkey ◽  
Martin Dugas ◽  
Julia Hauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Adhesion ◽  
Hematopoietic Cells ◽  
Promoter Regions ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
On Chip ◽  
Chip Analysis

Abstract Abstract 2486 Infants with t (7;12)/HLXB9-TEL positive Acute Myeloid Leukemia (AML) have an Event-Free Survival (EFS) of 0 % and are characterized by concomitant HLXB9 (MNX1) expression. However, the role of the homeobox protein HLXB9 on hematopoietic cell development remains unknown. Expression profiling of t (7;12) and t (11;X) positive leukemias revealed up-regulation of cell-cell interacting genes in t (7;12) positive leukemia (Wildenhain et al., 2010). Furthermore, no increased expression of HOX-Genes, like HOXA9 and MEIS1, could be observed in t (7;12) positive leukemia compared to t (11;X) positive leukemia. Based on the altered gene expression profile in t (7;12) positive leukemia we investigated the role of HLXB9 as a transcription factor in hematopoietic cells using ChIP-on-chip analysis and its impact on the cellular gene expression pattern using Affymetrix expression arrays. The myeloid cell line HL60 was stable transfected with a CMV-HLXB9 (HL60/HLXB9) expression vector or an empty vector control (HL60/control). Microarray analysis was performed using “Human Gene 1.0 ST Arrays” (Affymetrix) and data from the HL60/HLXB9 cells were normalized to HL60/control cells. ChIP-on-chip analysis was performed using the “SimpleChIP Enzymatic Chromatin IP Kit” (Cell Signaling Technologies). Hybridisation on “385K RefSeq Promoter arrays” and analysis of raw data were performed by NimbleGen using the NimbleScan software. Data were visualized with the SignalMap software. Altered expression analyses as well as enrichment of promoter regions were validated by quantitative RT-PCR. Expression analysis revealed 81 differentially expressed genes, whereof 63 were down-regulated indicating that HLXB9 acts as a transcriptional repressor, as characteristic for homeobox proteins. CLEC5A, normally expressed in mature myeloid cells, is the highest differentially repressed gene. Further, we identified several differentially expressed genes which interfere in cell-adhesion and/or angiogenesis (e.g. IL8, ZYX, SELL, SPP1, EMILIN2). Western blot analysis of nuclear extracts confirmed the translocation of HLXB9 into the nucleus. ChIP-on-chip analysis revealed binding of HLXB9 to several promoter regions, among them the promoters of ZYX and IL8. Binding of HLXB9 to those promoters results in a decreased gene expression.These data strengthens the hypothesis, that HLXB9 plays a major role in cell adhesion and/or cell interactions. Further we observed increased expression of the adhesion molecule CD11b, when culturing HL60/HLXB9 cells in All-Trans Retinoic Acid (ATRA) containing medium in contrast to HL60/control cells. In summary, this study shows that HLXB9 acts as a transcription factor in hematopoietic cells and has a repressive function on gene expression. HLXB9 target genes regulate cell-adhesion and angiogenesis. This study provides the first molecular results of HLXB9 function in hematopoietic cells and supports the previously published data showing the importance on altered gene expression of cell-cell interacting genes in the pathogenesis of t (7;12) positive leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Sexual Dimorphism in Growth Rate and Gene Expression Throughout Immature Development in Wild Type Chrysomya rufifacies (Diptera: Calliphoridae) Macquart

2021 ◽  
Vol 9 ◽  
Author(s):  
Meaghan L. Pimsler ◽  
Carl E. Hjelmen ◽  
Michelle M. Jonika ◽  
Anika Sharma ◽  
Shuhua Fu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Sex Determination ◽  
Splice Variants ◽  
Expression Patterns ◽  
Relevant Information ◽  
Wild Type ◽  
Chrysomya Rufifacies ◽  
Immature Development ◽  
Species Specific

Reliability of forensic entomology analyses to produce relevant information to a given case requires an understanding of the underlying arthropod population(s) of interest and the factors contributing to variability. Common traits for analyses are affected by a variety of genetic and environmental factors. One trait of interest in forensic investigations has been species-specific temperature-dependent growth rates. Recent work indicates sexual dimorphism may be important in the analysis of such traits and related genetic markers of age. However, studying sexual dimorphic patterns of gene expression throughout immature development in wild-type insects can be difficult due to a lack of genetic tools, and the limits of most sex-determination mechanisms. Chrysomya rufifacies, however, is a particularly tractable system to address these issues as it has a monogenic sex determination system, meaning females have only a single-sex of offspring throughout their life. Using modified breeding procedures (to ensure single-female egg clutches) and transcriptomics, we investigated sexual dimorphism in development rate and gene expression. Females develop slower than males (9 h difference from egg to eclosion respectively) even at 30°C, with an average egg-to-eclosion time of 225 h for males and 234 h for females. Given that many key genes rely on sex-specific splicing for the development and maintenance of sexually dimorphic traits, we used a transcriptomic approach to identify different expression of gene splice variants. We find that 98.4% of assembled nodes exhibited sex-specific, stage-specific, to sex-by-stage specific patterns of expression. However, the greatest signal in the expression data is differentiation by developmental stage, indicating that sexual dimorphism in gene expression during development may not be investigatively important and that markers of age may be relatively independent of sex. Subtle differences in these gene expression patterns can be detected as early as 4 h post-oviposition, and 12 of these nodes demonstrate homology with key Drosophila sex determination genes, providing clues regarding the distinct sex determination mechanism of C. rufifacies. Finally, we validated the transcriptome analyses through qPCR and have identified five genes that are developmentally informative within and between sexes.

scholarly journals DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon

2021 ◽  
Vol 9 ◽  
Author(s):  
Jolien Diddens ◽  
Louis Coussement ◽  
Carolina Frankl-Vilches ◽  
Gaurav Majumdar ◽  
Sandra Steyaert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Zebra Finch ◽  
Dosage Compensation ◽  
Expression Patterns ◽  
Song Learning ◽  
Sexually Dimorphic ◽  
Gene Expression Dynamics ◽  
Dimorphic Gene Expression

Song learning in zebra finches (Taeniopygia guttata) is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development. DNA methylation was very low, yet increased over time, particularly in song control nuclei. Only a small fraction of the massive differential expression in the developing zebra finch telencephalon could be explained by differential CpG and CpH DNA methylation. However, a strong association between DNA methylation and age-dependent gene expression was found for various transcription factors (i.e., OTX2, AR, and FOS) involved in neurodevelopment. Incomplete dosage compensation, independent of DNA methylation, was found to be largely responsible for sexually dimorphic gene expression, with dosage compensation increasing throughout life. In conclusion, our results indicate that DNA methylation regulates neurodevelopmental gene expression dynamics through steering transcription factor activity, but does not explain sexually dimorphic gene expression patterns in zebra finch telencephalon.

scholarly journals Transcriptome signature of miRNA-26b KO mouse model suggests novel targets

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Emiel P. C. van der Vorst ◽  
Mario A. A. Pepe ◽  
Linsey J. F. Peters ◽  
Markus Haberbosch ◽  
Yvonne Jansen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Blood Parameters ◽  
Exact Role ◽  
Neurological Processes ◽  
The Stability ◽  
Deficient Mice

Abstract Background MicroRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. Results A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. Conclusions miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies.

scholarly journals OP0045 NLRP12 INVOLVES IN THE LUPUS WITH POSITIVE INTERFERON SIGNATURE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
Y. P. Tsao ◽  
F. Y. Tseng ◽  
C. W. Chao ◽  
M. H. Chen ◽  
S. T. Chen
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Animal Models ◽  
Nucleic Acids ◽  
Disease Activity ◽  
Interferon Signature ◽  
Healthy Donors ◽  
Healthy Control ◽  
Lupus Disease Activity

Background:Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was recognized that interferon (IFN) signature involved in the progress of SLE. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. The importance of NLRP12 in lupus disease activity remained to be elucidated.Objectives:To clarify the role of NLRP12 in regulating the interferon signature.Methods:Peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors for analysis of NLRP12 and IFN-α gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed. Bone marrow derived dendritic cells (BMDCs) were collected from wild type mouse and Nlrp12 knocked-out mice. Another CD14+ monocytes were isolated from 10 cases of lupus patients and 8 cases of healthy control, following by stimulating different type of nucleic acids, and IFN-α and IL-6 were measured with ELISA assay. CD14+ monocytes in lupus patients were also pre-treated with IFNAR2 antibody for further nucleic acid stimulation. Two mice models were applied for evaluation the role of Nlrp12: intraperitoneal injection of TMPD (2,6,10,14-tetramethylpentadecane, or pristane) in C57BL/6 mice and Faslpr mice. Both models were conducted with and without Nlrp12 knockout.Results:NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. NLRP12 expression showed negative correlations with IFN-α treatment, as well as herpes simplex virus-1 (HSV-1) infection. Results from ChIP and EMSA analysis indicated a potential transcription factor 1 (TF-1) regulating NLRP12 promoter activity. TF-1 lead to transcriptional suppression of NLRP12 in SLE PBMC, and it was gradually induced after IFN treatment. Recruitment of TF-1 to NLRP12 promoter in SLE PBMC compared to the healthy PBMC was detected, and increased when treating with IFN. Human CD14+ monocytes collected from lupus and healthy control stimulating with different type of nucleic acids revealing significant increasing level of IFN-α and IL-6 in lupus patients. Among animal models, both pristine induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones, indicating the role of NLRP12 in maintaining positive interferon signature as well as disease activity.Conclusion:Expression level of NLRP1.2 has been demonstrated to be a biomarker of disease activity in SLE patients. The NLRP12 was involved in the interferon signature, which was also negatively regulated by TF-1. Both clinical samples and animal models revealed NLRP12 in maintaining the positive interferon signature, indicating the possible role of exacerbating factor for lupus disease activity.Disclosure of Interests:None declared

scholarly journals MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kulisara Marupanthorn ◽  
Chairat Tantrawatpan ◽  
Pakpoom Kheolamai ◽  
Duangrat Tantikanlayaporn ◽  
Sirikul Manochantr
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Osteogenic Differentiation ◽  
Differentiation Potential ◽  
Osteogenic Gene Expression ◽  
Osteogenic Gene

AbstractMesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

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