scholarly journals Repression of Virus-Induced Interferon A Promoters by Homeodomain Transcription Factor Ptx1

2000 ◽  
Vol 20 (20) ◽  
pp. 7527-7540 ◽  
Author(s):  
Sébastien Lopez ◽  
Marie-Laure Island ◽  
Jacques Drouin ◽  
Marie-Thérese Bandu ◽  
Nicolas Christeff ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Differential Expression ◽  
Antisense Rna ◽  
Differentially Express ◽  
Regulatory Element ◽  
Cell Types ◽  
Functional Feature ◽  
Homeodomain Transcription Factor ◽  
Responsive Element ◽  
Different Cell Types

ABSTRACT Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.

scholarly journals Differential Regulation of Human Interferon A Gene Expression by Interferon Regulatory Factors 3 and 7

2009 ◽  
Vol 29 (12) ◽  
pp. 3435-3450 ◽  
Author(s):  
Pierre Génin ◽  
Rongtuan Lin ◽  
John Hiscott ◽  
Ahmet Civas
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Transcriptional Activation ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Human Interferon ◽  
Gene Promoters ◽  
Nucleotide Substitutions ◽  
D Modules ◽  
Different Cell Types

ABSTRACT Differential expression of the human interferon A (IFN-A) gene cluster is modulated following paramyxovirus infection by the relative amounts of active interferon regulatory factor 3 (IRF-3) and IRF-7. IRF-3 expression activates predominantly IFN-A1 and IFN-B, while IRF-7 expression induces multiple IFN-A genes. IFN-A1 gene expression is dependent on three promoter proximal IRF elements (B, C, and D modules, located at positions −98 to −45 relative to the mRNA start site). IRF-3 binds the C module of IFN-A1, while other IFN-A gene promoters are responsive to the binding of IRF-7 to the B and D modules. Maximal expression of IFN-A1 is observed with complete occupancy of the three modules in the presence of IRF-7. Nucleotide substitutions in the C modules of other IFN-A genes disrupt IRF-3-mediated transcription, whereas a G/A substitution in the D modules enhances IRF7-mediated expression. IRF-3 exerts dual effects on IFN-A gene expression, as follows: a synergistic effect with IRF-7 on IFN-A1 expression and an inhibitory effect on other IFN-A gene promoters. Chromatin immunoprecipitation experiments reveal that transient binding of both IRF-3 and IRF-7, accompanied by CBP/p300 recruitment to the endogenous IFN-A gene promoters, is associated with transcriptional activation, whereas a biphasic recruitment of IRF-3 and CBP/p300 represses IFN-A gene expression. This regulatory mechanism contributes to differential expression of IFN-A genes and may be critical for alpha interferon production in different cell types by RIG-I-dependent signals, leading to innate antiviral immune responses.

Cell type-specific regulation of the Drosophila FMRF-NH2 neuropeptide gene by Apterous, a LIM homeodomain transcription factor

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4757-4765 ◽  
Author(s):  
R.J. Benveniste ◽  
S. Thor ◽  
J.B. Thomas ◽  
P.H. Taghert
Keyword(s):  
Transcription Factor ◽  
Morphological Differentiation ◽  
Cell Types ◽  
Neuroendocrine Cells ◽  
Cell Type ◽  
Homeodomain Transcription Factor ◽  
Neuron Survival ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Lim Homeodomain

We describe the direct and cell-specific regulation of the Drosophila FMRFa neuropeptide gene by Apterous, a LIM homeodomain transcription factor. dFMRFa and Apterous are expressed in partially overlapping subsets of neurons, including two of the seventeen dFMRFa cell types, the Tv neuroendocrine cells and the SP2 interneurons. Apterous contributes to the initiation of dFMRFa expression in Tv neurons, but not in those dFMRFa neurons that do not express Apterous. Apterous is not required for Tv neuron survival or morphological differentiation. Apterous contributes to the maintenance of dFMRFa expression by postembryonic Tv neurons, although the strength of its regulation is diminished. Apterous regulation of dFMRFa expression includes direct mechanisms, although ectopic Apterous does not induce ectopic dFMRFa. These findings show that, for a subset of neurons that share a common neurotransmitter phenotype, the Apterous LIM homeoprotein helps define neurotransmitter expression with very limited effects on other aspects of differentiation.

scholarly journals Isolation, sequence, and differential expression of a human K7 gene in simple epithelial cells.

1988 ◽  
Vol 107 (4) ◽  
pp. 1337-1350 ◽  
Author(s):  
C Glass ◽  
E Fuchs
Keyword(s):  
Epithelial Cells ◽  
Differential Expression ◽  
Molecular Mechanisms ◽  
Human Gene ◽  
Cell Types ◽  
Regulatory Elements ◽  
Gene Encoding ◽  
Keratin Gene ◽  
Base Level ◽  
Different Cell Types

Simple epithelial cells synthesize a different set of keratins than epidermal cells. In experiments reported in this manuscript, we show that the base level of keratin expression in simple epithelial cells is variable for different cell types, and that, in some simple epithelia, this level can be upregulated by increasing the exposure of cells to retinoids, but not glucocorticoids or estradiol. To elucidate the molecular mechanisms underlying simple epithelial keratin gene regulation, we have isolated and characterized a human gene encoding the simple epithelial keratin K7. By examining the possible regulatory elements of this gene and by investigating the behavior of this gene introduced transiently into simple epithelial cells, we have uncovered a possible basis for the differential expression of epidermal and simple epithelial keratin genes.

Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types

1991 ◽  
Vol 11 (3-4) ◽  
pp. 309-319 ◽  
Author(s):  
Zhengmin Huang ◽  
Douglas Thewke ◽  
Qingqing Gong ◽  
Doris Schlichter ◽  
Wesley D. Wicks
Keyword(s):  
Tyrosine Hydroxylase ◽  
Regulatory Element ◽  
Cell Types ◽  
Different Cell Types

scholarly journals Lmx1b influences correct post-mitotic coding of mesodiencephalic dopaminergic neurons

2018 ◽  
Author(s):  
Iris Wever ◽  
Pablo Largo Barrientos ◽  
Elisa J. Hoekstra ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factor ◽  
Dopaminergic Neurons ◽  
Cell Types ◽  
Late Development ◽  
Genetic Ablation ◽  
Depth Analysis ◽  
Homeobox Transcription Factor ◽  
Different Cell Types ◽  
Transcription Factor 1 ◽  
Inductive Activity

AbstractThe Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons.To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 levels were not altered in Lmx1b conditional knock-outs (cKO) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the VTA and SNc. Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.

Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family

1990 ◽  
Vol 10 (11) ◽  
pp. 5857-5864
Author(s):  
H van Dam ◽  
R Offringa ◽  
I Meijer ◽  
B Stein ◽  
A M Smits ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adenovirus Type ◽  
Cell Types ◽  
Transformation Process ◽  
Cell Type ◽  
Transcription Factor Family ◽  
Adenovirus E1a ◽  
E1a Gene ◽  
Responsive Element ◽  
Adenovirus Type 5

The adenovirus early region 1A (E1A) oncogene interferes with the expression level and activity of the AP-1 transcription factor family. E1A abolished the transactivating function of AP-1 (Jun/Fos), which binds to the 12-O-tetradecanoylphorbol-13-acetate-responsive element of the collagenase gene (collTRE). In contrast, the activity of another member of the AP-1 family that binds to the c-junTRE was not repressed. The mRNA expression of the c-jun gene was, in fact, strongly elevated in various cell types expressing the E1A gene of either adenovirus type 5 (Ad5) or Ad12. The regulation of the junB gene by adenovirus E1A, on the other hand, depended both on the cell type and on the transforming adenovirus serotype. The fact that E1A-induced alterations in the repertoire of AP-1 transcription factors depend on its transforming domain in conserved region 1 suggests that the effects are relevant for the transformation process.

scholarly journals CellBender remove-background: a deep generative model for unsupervised removal of background noise from scRNA-seq datasets

2019 ◽  
Author(s):  
Stephen J. Fleming ◽  
John C. Marioni ◽  
Mehrtash Babadi
Keyword(s):  
Differential Expression ◽  
Expression Profiles ◽  
Marker Gene ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Generative Model ◽  
Scalable Inference ◽  
Free Gene ◽  
Systematic Biases ◽  
Different Cell Types

AbstractDroplet-based scRNA-seq assays are known to produce a significant amount of background RNA counts, the hallmark of which is non-zero transcript counts in presumably empty droplets. The presence of background RNA can lead to systematic biases and batch effects in various downstream analyses such as differential expression and marker gene discovery. In this paper, we explore the phenomenology and mechanisms of background RNA generation in droplet-based scRNA-seq assays and present a deep generative model of background-contaminated counts mirroring those mechanisms. The model is used for learning the background RNA profile, distinguishing cell-containing droplets from empty ones, and retrieving background-free gene expression profiles. We implement the model along with a fast and scalable inference algorithm as the remove-background module in CellBender, an open-source scRNA-seq data processing software package. Finally, we present simulations and investigations of several scRNA-seq datasets to show that processing raw data using CellBender significantly boosts the magnitude and specificity of differential expression across different cell types.

scholarly journals Differential expression levels of Sox9 in early neocortical radial glial cells regulate the decision between stem cell maintenance and differentiation

2020 ◽  
Author(s):  
Jaime Fabra-Beser ◽  
Jessica Alves Medeiros de Araujo ◽  
Diego Marques-Coelho ◽  
Loyal A. Goff ◽  
Ulrich Müller ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Progenitor Cells ◽  
Differential Expression ◽  
Cortical Neurons ◽  
Expression Patterns ◽  
Neuronal Cell ◽  
Cell Types ◽  
Molecular Signature ◽  
Projection Neurons ◽  
Radial Glial

ABSTRACTRadial glial progenitor cells (RGCs) in the dorsal forebrain directly or indirectly produce excitatory projection neurons and macroglia of the neocortex. Recent evidence shows that the pool of RGCs is more heterogeneous than originally thought and that progenitor subpopulations can generate particular neuronal cell types. Using single cell RNA sequencing, we have studied gene expression patterns of two subtypes of RGCs that differ in their neurogenic behavior. One progenitor type rapidly produces postmitotic neurons, whereas the second progenitor remains relatively quiescence before generating neurons. We have identified candidate genes that are differentially expressed between these RGCs progenitor subtypes, including the transcription factor Sox9. Using in utero electroporation, we demonstrate that elevated Sox9 expression in progenitors prevents RGC division and leads to the generation of upper-layer cortical neurons from these progenitors at later ages. Our data thus reveal molecular differences between cortical progenitors with different neurogenic behavior and indicates that Sox9 is critical for the maintenance of RGCs to regulate the generation of upper layer neurons.SIGNIFICANCE STATEMENTThe existence of heterogeneity in the pool of RGCs and its relationship with the generation of cellular diversity in the cerebral cortex has been an interesting topic of debate for many years. Here we describe the existence of a subpopulation of RGCs with reduced neurogenic behavior at early embryonic ages presenting a particular molecular signature. This molecular signature consists of differential expression of some genes including the transcription factor Sox9, found to be a specific master regulator of this subpopulation of progenitor cells. Functional experiments perturbing Sox9 expression’s levels reveal its instructive role in the regulation of the neurogenic behavior of RGCs and its relationship with the generation of upper layer projection neurons at later ages.

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