scholarly journals Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Praveena L. Ramanujam ◽  
Sonam Mehrotra ◽  
Ram Parikshan Kumar ◽  
Shreekant Verma ◽  
Girish Deshpande ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Salivary Glands ◽  
Mammalian Cells ◽  
Target Genes ◽  
Ectopic Expression ◽  
Negative Regulator ◽  
Present Evidence ◽  
Mammalian Cell Lines ◽  
Context Dependent ◽  
Multiple Signaling

AbstractSpecial AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.

scholarly journals Sufu regulation of Hedgehog signaling in P19 cells is required for proper glial cell differentiation

2021 ◽  
Author(s):  
Danielle M. Spice ◽  
Joshua Dierolf ◽  
Gregory M. Kelly
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Glial Cell ◽  
Neural Differentiation ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Cell Model ◽  
Ectopic Expression ◽  
Negative Regulator ◽  
Embryonal Carcinoma Cell

AbstractHedgehog signaling is essential for vertebrate development, however, less is known about the negative regulators that influence this pathway during the differentiation of cell fates. Using the mouse P19 embryonal carcinoma cell model, Suppressor of Fused (SUFU), a negative regulator of the Hedgehog pathway, was investigated during retinoic acid-induced neural differentiation. We found Hedgehog signaling was activated in the early phase of neural differentiation and became inactive during terminal differentiation of neurons and astrocytes. SUFU, which regulates signaling at the level of GLI, remained relatively unchanged during the differentiation process, however SUFU loss through CRISPIR-Cas9 gene editing resulted in decreased cell proliferation and ectopic expression of Hedgehog target genes. Interestingly, SUFU-deficient cells were unable to differentiate in the absence of retinoic acid, but when differentiated in its presence they showed delayed and decreased astrocyte differentiation; neuron differentiation did not appear to be affected. Retinoic acid-induced differentiation also caused ectopic activation of Hh target genes in SUFU-deficient cells and while the absence of the GLI3 transcriptional inhibitor suggested the pathway was active, no full-length GLI3 was detected even though the message encoding Gli3 was present. Thus, the study would indicate the proper timing and proportion of glial cell differentiation requires SUFU, and its normal regulation of GLI3 to maintain Hh signaling in an inactive state.

Organization and Regulation of the Human Genome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-16-SCI-16
Author(s):  
Bing Ren
Keyword(s):  
Gene Regulation ◽  
Long Range ◽  
Genome Organization ◽  
Mammalian Cells ◽  
Target Genes ◽  
Critical Role ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Organization ◽  
Specific Gene

Abstract The 3-dimensional (3D) chromatin organization plays a critical role in gene regulation. Great strides have been made recently to characterize and identify cis regulatory elements from epigenome profiles in different cell types and tissues, but efforts have just begun to functionally characterize these long-range control elements. Mapping interactions between enhancers and promoters, and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of genome function. I will present recent findings related to 3D genome organization in mammalian cells, with a particular focus on how chromatin organization contributes to transcriptional regulation. I will describe higher-order organizational features that are observed at the level of both the whole chromosome and individual loci. I will highlight changes in genome organization that occur during the course of differentiation, and discuss the functional relationship between chromatin architecture and gene regulation. Taken together, mounting evidence now shows that the genome organization plays an essential role in orchestrating the lineage-specific gene expression programs through modulating long- range interactions between enhancers and target genes. Disclosures Ren: Arima Genomics, Inc.: Equity Ownership, Patents & Royalties; Eli Lilly: Employment.

A CCR4 Association Factor 1, OsCAF1B, Participates in the αAmy3 mRNA Poly(A) Tail Shortening and Plays a Role in Germination and Seedling Growth

2019 ◽  
Vol 61 (3) ◽  
pp. 554-564 ◽  
Author(s):  
Jhen-Cheng Fang ◽  
Hsin-Yi Liu ◽  
Yin-Chuan Tsai ◽  
Wei-Lun Chou ◽  
Chun-Chen Chang ◽  
...  
Keyword(s):  
Transgenic Rice ◽  
Seedling Growth ◽  
Mammalian Cells ◽  
Ectopic Expression ◽  
Mrna Degradation ◽  
Dominant Negative ◽  
Negative Regulator ◽  
Dominant Negative Mutation ◽  
Rate Limiting Step ◽  
Catabolite Repressor

Abstract Poly(A) tail (PAT) shortening, also termed deadenylation, is the rate-limiting step of mRNA degradation in eukaryotic cells. The carbon catabolite repressor 4-associated factor 1s (CAF1s) were shown to be one of the major enzymes for catalyzing mRNA deadenylation in yeast and mammalian cells. However, the functions of CAF1 proteins in plants are poorly understood. Herein, a sugar-upregulated CAF1 gene, OsCAF1B, is investigated in rice. Using gain–of–function and dominant-negative mutation analysis, we show that overexpression of OsCAF1B resulted in an accelerated α-amylase gene (αAmy3) mRNA degradation phenomenon, while ectopic expression of a form of OsCAF1B that had lost its deadenylase activity resulted in a delayed αAmy3 mRNA degradation phenomenon in transgenic rice cells. The change in αAmy3 mRNA degradation in transgenic rice is associated with the altered lengths of the αAmy3 mRNA PAT, indicating that OsCAF1B acts as a negative regulator of αAmy3 mRNA stability in rice. Additionally, we found that overexpression of OsCAF1B retards seed germination and seedling growth. These findings indicate that OsCAF1B participates in sugar-induced αAmy3 mRNA degradation and deadenylation and acts a negative factor for germination and seedling development.

scholarly journals Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells

2001 ◽  
Vol 21 (10) ◽  
pp. 3589-3597 ◽  
Author(s):  
Keri Fair ◽  
Melanie Anderson ◽  
Elena Bulanova ◽  
Huaifeng Mi ◽  
Maximilian Tropschug ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Target Gene ◽  
Target Genes ◽  
Leukemia Cells ◽  
Altered Expression ◽  
Amino Acid Sequence Conservation

ABSTRACT The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression ofHOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.

scholarly journals TRB3 Blocks Adipocyte Differentiation through the Inhibition of C/EBPβ Transcriptional Activity

2007 ◽  
Vol 27 (19) ◽  
pp. 6818-6831 ◽  
Author(s):  
Olivier Bezy ◽  
Cecile Vernochet ◽  
Stephane Gesta ◽  
Stephen R. Farmer ◽  
C. Ronald Kahn
Keyword(s):  
Mammalian Cells ◽  
Ectopic Expression ◽  
Negative Regulator ◽  
Biological Processes ◽  
Preadipocyte Differentiation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Important Negative Regulator ◽  
Regulatory Sites

ABSTRACT TRB3 has been implicated in the regulation of several biological processes in mammalian cells through its ability to influence Akt and other signaling pathways. In this study, we investigated the role of TRB3 in regulating adipogenesis and the activity of adipogenic transcription factors. We find that TRB3 is expressed in 3T3-L1 preadipocytes, and this expression is transiently suppressed during the initial days of differentiation concomitant with induction of C/EBPβ. This event appears to be a prerequisite for adipogenesis. Overexpression of TRB3 blocks differentiation of 3T3-L1 cells at a step downstream of C/EBPβ. Ectopic expression of TRB3 in mouse fibroblasts also inhibits the C/EBPβ-dependent induction of PPARγ2 and blocks their differentiation into adipocytes. This inhibition of preadipocyte differentiation by TRB3 appears to be the result of two complementary effects. First, TRB3 inhibits extracellular signal-regulated kinase activity, which prevents the phosphorylation of regulatory sites on C/EBPβ. Second, TRB3 directly interacts with the DR1 domain of C/EBPβ in the nucleus, further inhibiting both its ability to bind its response element and its ability to transactivate the C/EBPα and a-FABP promoters. Thus, TRB3 is an important negative regulator of adipogenesis that acts at an early step in the differentiation cascade to block the C/EBPβ proadipogenic function.

The conserved brassinosteroid-related transcription factor BIM1a negatively regulates fruit growth in tomato

2020 ◽  
Author(s):  
Kentaro Mori ◽  
Martine Lemaire-Chamley ◽  
Joana Jorly ◽  
Fernando Carrari ◽  
Mariana Conte ◽  
...  
Keyword(s):  
Target Genes ◽  
Fruit Size ◽  
Ectopic Expression ◽  
Negative Regulator ◽  
Crop Species ◽  
Signalling Network ◽  
Transgenic Lines ◽  
Related Transcription Factor ◽  
Fruit Pericarp

Abstract Brassinosteroids (BRs) are steroid hormones that play key roles in plant development and defense. Our goal is to harness the extensive knowledge of the Arabidopsis BR signalling network for improving productivity in crop species. This first requires identifying components of the conserved network and their function in the target species. Here, we investigated the function of SlBIM1a, the closest tomato homolog of AtBIM1, which is highly expressed in fruit. SlBIM1a overexpressing lines displayed severe plant and fruit dwarfism, and histological characterization of different transgenic lines revealed that SlBIM1a expression negatively correlated with fruit pericarp cell size, resulting in fruit size modifications. These growth phenotypes were in contrast to those found in Arabidopsis, and this was confirmed by the reciprocal ectopic expression of SlBIM1a/b in Arabidopsis and, AtBIM1 in tomato. These results determined that BIM1 function depends more on the recipient species than on its primary sequence. Yeast two-hybrid interaction studies and transcriptomic analyses of SlBIM1a overexpressing fruit, further suggested that SlBIM1a acts through its interaction with SlBZH1 to govern the transcriptional regulation of growth-related BRs target genes. Together, these results suggest that SlBIM1a is a negative regulator of pericarp cell expansion, possibly at the crossroad with auxin and light signalling.

Gene regulation by Sp1 and Sp3

2004 ◽  
Vol 82 (4) ◽  
pp. 460-471 ◽  
Author(s):  
Lin Li ◽  
Shihua He ◽  
Jian-Min Sun ◽  
James R Davie
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Dna Binding ◽  
Mammalian Cells ◽  
Cellular Localization ◽  
Target Genes ◽  
In Vivo Studies ◽  
Binding Domains

The Sp family of transcription factors is united by a particular combination of three conserved Cys2His2 zinc fingers that form the sequence-specific DNA-binding domain. Within the Sp family of transcription factors, Sp1 and Sp3 are ubiquitously expressed in mammalian cells. They can bind and act through GC boxes to regulate gene expression of multiple target genes. Although Sp1 and Sp3 have similar structures and high homology in their DNA binding domains, in vitro and in vivo studies reveal that these transcription factors have strikingly different functions. Sp1 and Sp3 are able to enhance or repress promoter activity. Regulation of the transcriptional activity of Sp1 and Sp3 occurs largely at the post-translational level. In this review, we focus on the roles of Sp1 and Sp3 in the regulation of gene expression.Key words: Sp1, Sp3, gene regulation, sub-cellular localization.

Evaluation of the nucleopolyhedrovirus of Anticarsia gemmatalis as a vector for gene therapy in mammals

2020 ◽  
Vol 20 ◽  
Author(s):  
Cintia N. Parsza ◽  
Diego L. Mengual Gómez ◽  
Jorge Alejandro Simonin ◽  
Mariano Nicolás Belaich ◽  
Pablo Daniel Ghiringhelli
Keyword(s):  
Gene Therapy ◽  
Mammalian Cells ◽  
Insect Cells ◽  
Autographa Californica ◽  
Anticarsia Gemmatalis ◽  
Agricultural Pests ◽  
Mammalian Cell Lines ◽  
Delivery Vector ◽  
Wide Range ◽  
Insect Pathogens

Background: Baculoviruses are insect pathogens with important biotechnological applications that transcend their use as biological controllers of agricultural pests. One species, Autographa californica multiple nucleopolhyedrovirus (AcMNPV) has been extensively exploited as a molecular platform to produce recombinant proteins and as a delivery vector for genes in mammals, because it can transduce a wide range of mammalian cells and tissues without replicating or producing progeny. Objective/Method: To investigate if the budded virions of Anticarsia gemmatalis multiple nucleopolhyedrovirus (AgMNPV) species has the same ability, the viral genome was modified by homologous recombination into susceptible insect cells to integrate reporter genes and then it was evaluated on mammalian cell lines in comparative form with respect to equivalent viruses derived from AcMNPV. Besides, the replicative capacity of AgMNPV´s virions in mammals was determined. Results: The experiments carried out showed that the recombinant variant of AgMNPV transduces and support the expression of delivered genes but not replicates in mammalian cells. Conclusion: Consequently, this insect pathogen is proposed as an alternative of non-infectious viruses in humans to explore new approaches in gene therapy and other applications based on the use of mammalian cells.

The SNPs within 3'UTR of miRNA Target Genes Related to Multiple Sclerosis: A Computational Prediction

2020 ◽  
Vol 17 (2) ◽  
pp. 133-147
Author(s):  
Mina Zafarpiran ◽  
Roya Sharifi ◽  
Zeinab Shirvani-Farsani
Keyword(s):  
Multiple Sclerosis ◽  
Gene Regulation ◽  
Binding Sites ◽  
Target Genes ◽  
Demyelinating Disease ◽  
Target Prediction ◽  
Computational Prediction ◽  
Functional Verification ◽  
Candidate Snps ◽  
Inflammatory Genes

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system, and genetic factors play an important role in its susceptibility. The expressions of many inflammatory genes implicated in MS are regulated by microRNA (miRNAs), whose function is to suppress the translation by pairing with miRNA Recognition Elements (MREs) present in the 3' untranslated region (3'UTR) of target mRNA. Recently, it has been shown that the Single Nucleotide Polymorphism (SNPs) present within the 3'UTR of mRNAs can affect the miRNA-mediated gene regulation and susceptibility to a variety of human diseases. Objective: The aim of this study was to analyze the SNPs within the 3'UTR of miRNA inflammatory target genes related to multiple sclerosis. Methods: By DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases, 3'UTR genetic variants were identified in all inflammatory genes associated with MS. Also, miRNA's target prediction databases were used for predicting the miRNA binding sites. Results: We identified 125 SNPs with MAF>0.05 located in the binding site of the miRNA of 35 genes among 59 inflammatory genes related to MS. Bioinformatics analysis predicted 62 MRE-modulating SNPs and 59 MRE-creating SNPs in the 3'UTR of MSimplicated inflammatory genes. These candidate SNPs within miRNA binding sites of inflammatory genes can alter the miRNAs binding, and consequently lead to the mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in personalized medicine of MS, and hence, they would be valuable for further functional verification investigations.

scholarly journals .BETA.-Adrenergic effects on salivary glands: Growth and gene regulation.

1990 ◽  
Vol 23 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Setsuya Fujita ◽  
Tsukasa Ashihara ◽  
TIBOR BARKA
Keyword(s):  
Gene Regulation ◽  
Salivary Glands ◽  
Beta Adrenergic ◽  
Adrenergic Effects
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