Transcriptional regulation of the HO-1 gene in cultured macrophages exposed to model airborne particulate matter

2003 ◽  
Vol 284 (3) ◽  
pp. L473-L480 ◽  
Author(s):  
Beek Yoke Chin ◽  
Michael A. Trush ◽  
Augustine M. K. Choi ◽  
Terence H. Risby
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Particulate Matter ◽  
Mutational Analysis ◽  
Regulatory Element ◽  
Airborne Particulate Matter ◽  
Regulatory Elements ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Respirable Particulate

Respirable particulate matter generated during incomplete combustion of fossil fuels may principally target the cells found in the distal region of the lung. This study characterizes some of the effects that a model particulate matter has on the induction of heme oxygenase (HO)-1 in macrophages. HO-1 is a highly inducible stress response gene that has been demonstrated to modulate chemical, physical, and environmental stimuli. Cultured macrophages (RAW 264.7 cells) exposed continuously to a well-defined model of particulate matter (benzo[ a]pyrene adsorbed onto carbon black) induced HO-1 gene expression in a time-dependent manner. Likewise, the addition of benzo[ a]pyrene-1,6-quinone, a redox cycling metabolite of benzo[ a]pyrene, to RAW cells also induced HO-1. This particle-induced gene expression of HO-1 was found to correlate with a corresponding increase in protein levels. Gene regulation studies were performed to delineate the transcriptional regulation of HO-1 after exposure to model particulate matter. Deletional analysis of the HO-1 gene and mutational analysis of activator protein (AP)-1 regulatory element on both distal enhancers demonstrated the importance of this transcriptional factor in mediating HO-1 gene transcription in response to model particulate matter. These results were supported by gel shift analysis demonstrating increased AP-1 binding activity after exposure to particulate matter. In summary, this study demonstrates that model particulate matter enhanced the expression of HO-1. This inductive process may be mediated by AP-1 activation of the regulatory elements on both the 5′-distal enhancers.

scholarly journals The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
José L Ruiz ◽  
Lisa C Ranford-Cartwright ◽  
Elena Gómez-Díaz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Anopheles Gambiae ◽  
Mosquito Control ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Malaria Vectors ◽  
Specific Gene ◽  
Mosquito Vector ◽  
Human Malaria

Abstract Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by the assay for transposase-accessible chromatin by sequencing (ATAC-seq) in laboratory-reared A. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data, we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue-specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that were annotated to mosquito immune-related genes. Not only is this study important for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but the information we produced also has great potential for developing new mosquito-control and anti-malaria strategies.

scholarly journals A gain-of-function single nucleotide variant creates a new promoter which acts as an orientation-dependent enhancer-blocker

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yavor K. Bozhilov ◽  
Damien J. Downes ◽  
Jelena Telenius ◽  
A. Marieke Oudelaar ◽  
Emmanuel N. Olivier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Base Change ◽  
Dependent Manner ◽  
Globin Genes ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Super Enhancer ◽  
Single Base Change

AbstractMany single nucleotide variants (SNVs) associated with human traits and genetic diseases are thought to alter the activity of existing regulatory elements. Some SNVs may also create entirely new regulatory elements which change gene expression, but the mechanism by which they do so is largely unknown. Here we show that a single base change in an otherwise unremarkable region of the human α-globin cluster creates an entirely new promoter and an associated unidirectional transcript. This SNV downregulates α-globin expression causing α-thalassaemia. Of note, the new promoter lying between the α-globin genes and their associated super-enhancer disrupts their interaction in an orientation-dependent manner. Together these observations show how both the order and orientation of the fundamental elements of the genome determine patterns of gene expression and support the concept that active genes may act to disrupt enhancer-promoter interactions in mammals as in Drosophila. Finally, these findings should prompt others to fully evaluate SNVs lying outside of known regulatory elements as causing changes in gene expression by creating new regulatory elements.

scholarly journals Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early gene expression via CArG elements.

1990 ◽  
Vol 10 (8) ◽  
pp. 4243-4255 ◽  
Author(s):  
D Gius ◽  
X M Cao ◽  
F J Rauscher ◽  
D R Cohen ◽  
T Curran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Early Gene ◽  
Immediate Early ◽  
Striking Similarity ◽  
Independent Functions

The Fos-Jun complex has been shown to activate transcription through the regulatory element known as the AP-1 binding site. We show that Fos down regulates several immediate-early genes (c-fos, Egr-1, and Egr-2) after mitogenic stimulation. Specifically, we demonstrate that the target for this repression is a sequence of the form CC(A/T)6GG, also known as a CArG box. Whereas Fos bound to the AP-1 site through a domain rich in basic amino acids and associated with Jun via a leucine zipper interaction, mutant Fos proteins lacking these structures were still capable of causing repression. Furthermore, Jun neither enhanced nor inhibited down regulation by Fos. Critical residues required for repression are located within the C-terminal 27 amino acids of c-Fos, since v-Fos and C-terminal truncations of c-Fos did not down regulate. In addition, transfer of 180 c-Fos C-terminal amino acids to Jun conferred upon it the ability to repress. Finally, Fra-1, a Fos-related protein which has striking similarity to Fos in its C-terminal 40 amino acids, also down regulated Egr-1 expression. Thus, Fos is a transcriptional regulator that can activate or repress gene expression by way of two separate functional domains that act on distinct regulatory elements.

scholarly journals Airborne Particulate Matter Density in Traditional Bakeries of Saveh, Central of Iran, in 2020

2020 ◽  
Author(s):  
Edris Hoseinzadeh ◽  
Mehrzad Ghorbani ◽  
Mahdi Safari ◽  
Najmeh Ebrahimi
Keyword(s):  
Particulate Matter ◽  
Particle Concentration ◽  
Gravimetric Method ◽  
Airborne Particulate Matter ◽  
High Concentration ◽  
Cross Sectional ◽  
Flour Dust ◽  
Average Size ◽  
High Level ◽  
Respirable Particulate

Introduction: High concentration of inhalable airborne particles can increase the risk of lung disease in exposed people. This study aimed to determine the respirable particulate matter (PM5) concentration in traditional bakeries of Saveh in 2020. Materials and Methods: This cross-sectional descriptive study was conducted among 25 bakeries where the samples were collected by cyclone and teflon filter equipped by air sampling pump. Later, the respirable particulate matter concentration was measured using gravimetric method. The collected PM5 was scanned using a FTIR (Fourier-transform infrared spectroscopy) with regard to flour dust. In addition, size and shape of the collected PM5 were analyzed using a scanning electron microscope (SEM). Results: Findings showed that the Lavash bakery had the highest PM5 concentration (9.15 mg/m3) in comparison with two other bakeries (Sangak and Barbari). However, an inverse relationship was observed between RH and particle concentration. In addition, the results demonstrated that increasing RH decreased the particle concentration, but the relationship was not significant (P = 0.052, Spearman's rho = -0.393). Furthermore, Lavash bakery had the lowest average size of PM5 (0.63 ± 0.32 μm). However, the FTIR scans confirmed that the flour dust had the predominant amount of PM5. Conclusion: Based on the findings, the density of respirable PM5 has a high level in Saveh bakeries and workers  are exposed to high levels of PM.

Induction of apoptosis by particulate matter: role of TNF-α and MAPK

1998 ◽  
Vol 275 (5) ◽  
pp. L942-L949 ◽  
Author(s):  
Beek Yoke Chin ◽  
Mary E. Choi ◽  
Marie D. Burdick ◽  
Robert M. Strieter ◽  
Terence H. Risby ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Carbon Black ◽  
Mapk Pathway ◽  
Time Dependent ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Mapk Kinase ◽  
Tnf Α ◽  
Induced Apoptosis

Particulate matter (PM) is a major by-product from the combustion of fossil fuels. The biological target of inhaled PM is the pulmonary epithelium and resident macrophages. In this study, we demonstrate that cultured macrophages (RAW 264.7 cells) exposed continously to a well-defined model of PM [benzo[ a]pyrene adsorbed on carbon black (CB+BaP)] exhibit a time-dependent expression and release of the cytokine tumor necrosis factor-α (TNF-α). CB+BaP also evoked programmed cell death or apoptosis in cultured macrophages as assessed by genomic DNA-laddering assays. The CB+BaP-induced apoptosis was inhibited when macrophages were treated with CB+BaP in the presence of a neutralizing antibody to TNF-α, suggesting that TNF-α plays an important role in mediating CB+BaP-induced apoptosis in macrophages. Interestingly, neither untreated carbon black nor benzo[ a]pyrene alone induced apoptosis or caused the release of TNF-α in RAW 264.7 cells. Moreover, we observed that TNF-α activates mitogen-activated protein kinase (MAPK) activity, the extracellular signal-regulated kinases p42/p44, in a time-dependent manner. RAW 264.7 cells treated with PD-098059, a selective inhibitor of MAPK kinase activity, did not exhibit CB+BaP-induced apoptosis and TNF-α secretion. Furthermore, cells treated with the MAPK kinase inhibitor did not undergo TNF-α-induced apoptosis. Taken together, our data suggest that TNF-α mediates PM-induced apoptosis and that the MAPK pathway may play an important role in regulating this pathway.

scholarly journals Epigenomic landscape of enhancer elements during Hydra head organizer formation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Puli Chandramouli Reddy ◽  
Akhila Gungi ◽  
Suyog Ubhe ◽  
Sanjeev Galande
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Histone Modifications ◽  
Specific Inhibitor ◽  
Regulatory Elements ◽  
The Body ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Chromatin Architecture ◽  
Ectopic Activation

Abstract Background Axis patterning during development is accompanied by large-scale gene expression changes. These are brought about by changes in the histone modifications leading to dynamic alterations in chromatin architecture. The cis regulatory DNA elements also play an important role towards modulating gene expression in a context-dependent manner. Hydra belongs to the phylum Cnidaria where the first asymmetry in the body plan was observed and the oral-aboral axis originated. Wnt signaling has been shown to determine the head organizer function in the basal metazoan Hydra. Results To gain insights into the evolution of cis regulatory elements and associated chromatin signatures, we ectopically activated the Wnt signaling pathway in Hydra and monitored the genome-wide alterations in key histone modifications. Motif analysis of putative intergenic enhancer elements from Hydra revealed the conservation of bilaterian cis regulatory elements that play critical roles in development. Differentially regulated enhancer elements were identified upon ectopic activation of Wnt signaling and found to regulate many head organizer specific genes. Enhancer activity of many of the identified cis regulatory elements was confirmed by luciferase reporter assay. Quantitative chromatin immunoprecipitation analysis upon activation of Wnt signaling further confirmed the enrichment of H3K27ac on the enhancer elements of Hv_Wnt5a, Hv_Wnt11 and head organizer genes Hv_Bra1, CnGsc and Hv_Pitx1. Additionally, perturbation of the putative H3K27me3 eraser activity using a specific inhibitor affected the ectopic activation of Wnt signaling indicating the importance of the dynamic changes in the H3K27 modifications towards regulation of the genes involved in the head organizer activity. Conclusions The activation-associated histone marks H3K4me3, H3K27ac and H3K9ac mark chromatin in a similar manner as seen in bilaterians. We identified intergenic cis regulatory elements which harbor sites for key transcription factors involved in developmental processes. Differentially regulated enhancers exhibited motifs for many zinc-finger, T-box and ETS related TFs whose homologs have a head specific expression in Hydra and could be a part of the pioneer TF network in the patterning of the head. The ability to differentially modify the H3K27 residue is critical for the patterning of Hydra axis revealing a dynamic acetylation/methylation switch to regulate gene expression and chromatin architecture.

scholarly journals Targeted inactivation of the major positive regulatory element (HS-40) of the human alpha-globin gene locus

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1202-1211 ◽  
Author(s):  
A Bernet ◽  
S Sabatier ◽  
DJ Picketts ◽  
R Ouazana ◽  
F Morle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Locus ◽  
Regulatory Element ◽  
Globin Gene ◽  
Marker Gene ◽  
Regulatory Elements ◽  
Target System ◽  
Flp Recombinase ◽  
Alpha Globin ◽  
Globin Gene Expression

Abstract We have examined the role of the major positive upstream regulatory element of the human alpha-globin gene locus (HS-40) in its natural chromosomal context. Using homologous recombination, HS-40 was replaced by a neo marker gene in a mouse erythroleukemia hybrid cell line containing a single copy of human chromosome 16. In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected. Deletion of the neo marker gene, by using FLP recombinase/FLP recombinase target system, proved that the phenotype observed was not caused by the regulatory elements of this marker gene. In the targeted clones, deletion of HS-40 apparently does not affect long-range or local chromatin structure at the alpha promoters. Therefore, these results indicate that, in the experimental system used, HS-40 behaves as a strong inducible enhancer of human alpha- globin gene expression.

scholarly journals Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei.

1995 ◽  
Vol 15 (11) ◽  
pp. 5945-5956 ◽  
Author(s):  
S V Graham ◽  
J D Barry
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Life Cycle ◽  
Life Cycle Stage ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Mammalian Host ◽  
Dependent Manner ◽  
African Trypanosomes ◽  
Specific Subset

In antigenic variation in African trypanosomes, switching of the variant surface glycoprotein (VSG) allows evasion of the mammalian host immune response. Trypanosomes first express the VSG in the tsetse fly vector, at the metacyclic stage, in preparation for transfer into the mammal. In this life cycle stage, a small, specific subset (1 to 2%) of VSGs are activated, and we have shown previously that the system of activation and expression of metacyclic VSG (M-VSG) genes is very different from that used for bloodstream VSG genes (S.V. Graham, K.R. Matthews, P.G. Shiels, and J.D. Barry, Parasitology 101:361-367, 1990). Now we show that unlike other trypanosome genes including bloodstream VSG genes, M-VSG genes are expressed from promoters subject to exclusively transcriptional regulation in a life cycle stage-dependent manner. We have located an M-VSG gene promoter, and we demonstrate that it is specifically up-regulated at the metacyclic stage. This is the first demonstration of gene expression being regulated entirely at the level of transcription among the Kinetoplastida; all other protein-coding genes examined in these organisms are, at least partly, under posttranscriptional control. The distinctive mode of expression of M-VSG genes may be due to a stochastic mechanism for metacyclic VSG activation.

scholarly journals Transcriptional Activation of the Decidual/Trophoblast Prolactin-Related Protein Gene1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4032-4039 ◽  
Author(s):  
Kyle E. Orwig ◽  
Michael J. Soares
Keyword(s):  
Transcriptional Activation ◽  
Promoter Activity ◽  
Mutational Analysis ◽  
Regulatory Element ◽  
Gene Activation ◽  
Cell Formation ◽  
Regulatory Elements ◽  
Related Protein ◽  
Trophoblast Cells ◽  
Decidual Cells

Abstract The decidual/trophoblast PRL-related protein (d/tPRP) is dually expressed by decidual and trophoblast cells during pregnancy. We have characterized the proximal d/tPRP promoter responsible for directing d/tPRP expression in decidual and trophoblast cells. We have demonstrated that the proximal 93 bp of d/tPRP 5′-flanking DNA are sufficient to direct luciferase gene expression in primary decidual and Rcho-1 trophoblast cells, but not in fibroblast, undifferentiated uterine stromal cells or trophoblast cells of a labyrinthine lineage. The 93-bp d/tPRP promoter was also sufficient to direct differentiation-dependent expression in trophoblast giant cells. Mutational analysis demonstrated the differential importance of activating protein-1 and Ets regulatory elements (located within the proximal 93 bp of d/tPRP 5′-flanking DNA) for activation of the d/tPRP promoter in decidual vs. trophoblast cells. Disruption of the activating protein-1 regulatory element inhibited d/tPRP promoter activity by more than 95% in decidual cells, and approximately 80% trophoblast cells. Disruption of the Ets regulatory element reduced d/tPRP promoter activity by approximately 50% in decidual cells, while inactivating the d/tPRP promoter in trophoblast cells. Protein interactions with the trophoblast Ets regulatory element were shown to be cell type specific and to change during trophoblast giant cell formation. In conclusion, a 93-bp region of the d/tPRP promoter is shown to contain regulatory elements sufficient for gene activation in decidual and trophoblast cells.

Sign in / Sign up

Export Citation Format

Share Document