scholarly journals Cell-type–specific transcriptional regulation of PIGM underpins the divergent hematologic phenotype in inherited GPl deficiency

Blood ◽  
2014 ◽  
Vol 124 (20) ◽  
pp. 3151-3154 ◽  
Author(s):  
Joana R. Costa ◽  
Valentina S. Caputo ◽  
Kalliopi Makarona ◽  
D. Mark Layton ◽  
Irene A. G. Roberts ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
B Cells ◽  
Core Promoter ◽  
Red Cells ◽  
Cell Type ◽  
Promoter Mutation ◽  
The Core ◽  
Key Points ◽  
Cell Type Specific ◽  
Core Promoter Mutation

Key Points B cells but not red cells are GPI deficient in PIGM-associated IGD, caused by a core promoter mutation that abrogates Sp1 binding. In red but not B cells, PIGM transcription is independent of Sp1 binding to the core promoter, hence GPI expression in red cells is near normal.

Endothelial-cell-specific regulation of von Willebrand factor gene expression

1994 ◽  
Vol 14 (2) ◽  
pp. 999-1008
Author(s):  
N Jahroudi ◽  
D C Lynch
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Core Promoter ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Specific Gene ◽  
Cell Type ◽  
The Core ◽  
Cell Type Specific ◽  
Von Willebrand

In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothelial-cell-specific gene expression. In this study, deletion analyses were carried out to identify the region of the vWf gene which regulates its endothelial-cell-specific expression. A 734-bp fragment which spans the sequence from -487 to +247 relative to the transcription start site was identified as the cell-type-specific promoter. It consists of a minimal core promoter located between -90 and +22, a strong negative regulatory element located upstream of the core promoter (ca. -500 to -300), and a positive regulatory region located downstream of the core promoter in the first exon. The activity of the core promoter is not cell type specific, and the negative regulatory region is required to inhibit its activity in all cell types. The positive regulatory region relieves this inhibition only in endothelial cells and results in endothelial-cell-specific gene expression. The positive regulatory region contains sequences predicting possible SP1, GATA, and octamer binding sites. Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner.

scholarly journals Endothelial-cell-specific regulation of von Willebrand factor gene expression.

1994 ◽  
Vol 14 (2) ◽  
pp. 999-1008 ◽  
Author(s):  
N Jahroudi ◽  
D C Lynch
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Core Promoter ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Specific Gene ◽  
Cell Type ◽  
The Core ◽  
Cell Type Specific ◽  
Von Willebrand

In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothelial-cell-specific gene expression. In this study, deletion analyses were carried out to identify the region of the vWf gene which regulates its endothelial-cell-specific expression. A 734-bp fragment which spans the sequence from -487 to +247 relative to the transcription start site was identified as the cell-type-specific promoter. It consists of a minimal core promoter located between -90 and +22, a strong negative regulatory element located upstream of the core promoter (ca. -500 to -300), and a positive regulatory region located downstream of the core promoter in the first exon. The activity of the core promoter is not cell type specific, and the negative regulatory region is required to inhibit its activity in all cell types. The positive regulatory region relieves this inhibition only in endothelial cells and results in endothelial-cell-specific gene expression. The positive regulatory region contains sequences predicting possible SP1, GATA, and octamer binding sites. Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner.

scholarly journals Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner

2021 ◽  
Author(s):  
Guoxun Wang ◽  
Christina Zarek ◽  
Tyron Chang ◽  
Lili Tao ◽  
Alexandria Lowe ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Types ◽  
The Body ◽  
Receptor Expression ◽  
Conditional Knockout ◽  
Interleukin 4 ◽  
Virus Reactivation ◽  
Cell Type ◽  
Murine Gammaherpesvirus ◽  
Cell Type Specific

Gammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi’s sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation, but that it was dispensable on B cells. We further demonstrated that the transcription factor, STAT6, which is downstream of the IL-4 receptor and binds virus gene 50 N4/N5 promoter in macrophages, did not bind to the virus gene 50 N4/N5 promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may only affect latent virus in particular cell types, but not in others. Importance Herpesviruses establish life-long quiescent infections in specific cells in the body, and only reactivate to produce infectious virus when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus. However, herpesviruses establish latency in multiple cell types in their hosts. Using murine gammaherpesvirus-68 (MHV68) and conditional knockout mice, we examined the cell type specificity of a particular reactivation signal, interleukin-4 (IL-4). We found that IL-4 only induced herpesvirus reactivation from macrophages, but not from B cells. This work indicates that regulation of virus latency and reactivation is cell type specific. This has important implications for therapies aimed at either promoting or inhibiting reactivation for the control or elimination of chronic viral infections.

scholarly journals Identification and characterization of cis-regulatory elements for photoreceptor type-specific transcription in zebrafish

2019 ◽  
Author(s):  
Wei Fang ◽  
Yi Wen ◽  
Xiangyun Wei
Keyword(s):  
Core Promoter ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Protein Coding ◽  
Core Promoters ◽  
Protein Coding Genes ◽  
The Core ◽  
Cell Type Specific ◽  
Identification And Characterization

AbstractTissue-specific or cell type-specific transcription of protein-coding genes is controlled by both trans-regulatory elements (TREs) and cis-regulatory elements (CREs). However, it is challenging to identify TREs and CREs, which are unknown for most genes. Here, we describe a protocol for identifying two types of transcription-activating CREs—core promoters and enhancers—of zebrafish photoreceptor type-specific genes. This protocol is composed of three phases: bioinformatic prediction, experimental validation, and characterization of the CREs. To better illustrate the principles and logic of this protocol, we exemplify it with the discovery of the core promoter and enhancer of the mpp5b apical polarity gene (also known as ponli), whose red, green, and blue (RGB) cone-specific transcription requires its enhancer, a member of the rainbow enhancer family. While exemplified with an RGB cone-specific gene, this protocol is general and can be used to identify the core promoters and enhancers of other protein-coding genes.

scholarly journals Conserved gammaherpesvirus protein kinase counters the antiviral effects of myeloid cell specific STAT1 expression to promote the establishment of splenic B cell latency.

2021 ◽  
Author(s):  
P. A. Sylvester ◽  
C. N. Jondle ◽  
K. P. Stoltz ◽  
J. Lanham ◽  
B. N. Dittel ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Protein Kinase ◽  
B Cell ◽  
Latent Reservoir ◽  
Type I ◽  
B Cell Differentiation ◽  
Cell Type ◽  
Antiviral Effects ◽  
Cell Type Specific

Gammaherpesviruses establish life-long infections and are associated with B cell lymphomas. Murine gammaherpesvirus-68 (MHV68) infects epithelial and myeloid cells during acute infection, with subsequent passage of the virus to B cells, where physiological B cell differentiation is usurped to ensure the establishment of chronic latent reservoir. Interferons (IFNs) represent a major antiviral defense system that engages transcriptional factor STAT1 to attenuate diverse acute and chronic viral infections, including those of gammaherpesviruses. Correspondingly, global deficiency of type I or type II IFN signaling profoundly increases the pathogenesis of acute and chronic gammaherpesvirus infection, compromises host survival, and impedes mechanistic understanding of cell type-specific role of IFN signaling. Here we demonstrate that myeloid-specific STAT1 deficiency attenuates acute and persistent MHV68 replication in the lungs and suppresses viral reactivation from peritoneal cells, without any effect on the establishment of viral latent reservoir in splenic B cells. All gammaherpesviruses encode a conserved protein kinase that antagonizes type I IFN signaling in vitro. Here, we show that myeloid-specific STAT1 deficiency rescues the attenuated splenic latent reservoir of kinase null MHV68 mutant. However, despite having gained access to splenic B cells, protein kinase null MHV68 mutant fails to drive B cell differentiation. Thus, while myeloid-intrinsic STAT1 expression must be counteracted by the gammaherpesvirus protein kinase to facilitate viral passage to splenic B cells, expression of the viral protein kinase continues to be required to promote optimal B cell differentiation and viral reactivation, highlighting the multifunctional nature of this conserved viral protein during chronic infection. Importance. IFN signaling is a major antiviral system of the host that suppresses replication of diverse viruses, including acute and chronic gammaherpesvirus infection. STAT1 is a critical member and the primary antiviral effector of IFN signaling pathways. Given the significantly compromised antiviral status of global type I or type II IFN deficiency, unabated gammaherpesvirus replication and pathogenesis hinders understanding of cell type-specific antiviral effects. In this study, a mouse model of myeloid-specific STAT1 deficiency unveiled site-specific antiviral effects of STAT1 in the lungs and peritoneal cavity, but not spleen of chronically infected hosts. Interestingly, expression of a conserved gammaherpesvirus protein kinase was required to counteract the antiviral effects of myeloid-specific STAT1 expression to facilitate latent infection of splenic B cells, revealing a cell-type specific virus-host antagonism during the establishment of chronic gammaherpesvirus infection.

Cell type-specific transcriptional regulation of the drosophila FMRFamide neuropeptide gene

Neuron ◽  
1993 ◽  
Vol 10 (2) ◽  
pp. 279-291 ◽  
Author(s):  
Lynne E. Schneider ◽  
Marie S. Roberts ◽  
Paul H. Taghert
Keyword(s):  
Transcriptional Regulation ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the β-globin locus

2012 ◽  
Vol 40 (16) ◽  
pp. 7718-7727 ◽  
Author(s):  
Ivan Junier ◽  
Ryan K. Dale ◽  
Chunhui Hou ◽  
François Képès ◽  
Ann Dean
Keyword(s):  
Transcriptional Regulation ◽  
Chromosome Organization ◽  
Cell Type ◽  
Specific Chromosome ◽  
Cell Type Specific

Which is the best predictor of hepatitis activity in HBeAg-negative patients: Alanine transaminase (ALT), HBV DNA, Pre-Core/Core promoter mutation or viral genotypes?

2001 ◽  
Vol 120 (5) ◽  
pp. A554-A555 ◽  
Author(s):  
Joseph J.Y. Sung ◽  
Henry L.Y. Chan ◽  
May L. Wong ◽  
Chi-Hang Tse ◽  
John S.I. Tam ◽  
...  
Keyword(s):  
Core Promoter ◽  
Hbv Dna ◽  
Alanine Transaminase ◽  
Promoter Mutation ◽  
Core Promoter Mutation

scholarly journals Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes

Blood ◽  
2014 ◽  
Vol 124 (25) ◽  
pp. 3719-3729 ◽  
Author(s):  
Jason S. Weinstein ◽  
Kimberly Lezon-Geyda ◽  
Yelena Maksimova ◽  
Samuel Craft ◽  
Yaoping Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Cell Function ◽  
Cell Type ◽  
Effector Cells ◽  
T Effector Cells ◽  
Follicular Helper ◽  
Key Points ◽  
Cell Type Specific ◽  
Global Transcriptome

Key Points Transcriptomes and enhancers of human CD4+ Tfh and non-Tfh T effector cells reveal cell type–specific differences. These data are a significant resource for understanding mechanisms of normal and perturbed Tfh cell function.

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