scholarly journals Transcriptional control of IFNT expression

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F21-F31 ◽  
Author(s):  
Toshihiko Ezashi ◽  
Kazuhiko Imakawa
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Intracellular Signaling ◽  
Transcriptional Control ◽  
Proximal Region ◽  
Type I ◽  
Interferon Tau ◽  
Specific Expression ◽  
Uterine Endometrium ◽  
Separate Site

Once interferon-tau (IFNT) had been identified as a type I IFN in sheep and cattle and its functions were characterized, numerous studies were conducted to elucidate the transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5′UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA-binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT downregulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.

Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription factor Spi-1/PU.1.

1995 ◽  
Vol 15 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Y Kominato ◽  
D Galson ◽  
W R Waterman ◽  
A C Webb ◽  
P E Auron
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Reporter Gene ◽  
Expression Vector ◽  
Dominant Negative ◽  
Specific Factor ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Interleukin-1 beta (IL-1 beta) is produced primarily by stimulated monocytes, suggesting that the IL1B gene, which codes for this protein, depends upon at least one cell-type-specific factor. Our previous characterization of the IL1B promoter indicated that the region between -131 and +12 is sufficient to direct cell-type-specific expression of a reporter gene (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M.J. Fenton, A.C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). We now show that a sequence located between positions -50 and -39 of the IL1B promoter binds the tissue-restricted Ets domain transcription factor Spi-1/PU.1 (Spi-1). Mutation of this site abrogates binding of this factor and reduces the ability of the IL1B promoter to function in macrophages. A second Spi-1 binding site located between positions -115 and -97 also is required for maximal IL1B promoter activity in the presence of the proximal Spi-1 binding site. In addition, an activation domain-deficient Spi-1 expression vector acts as a dominant-negative inhibitor of reporter gene expression in a monocyte cell line. Finally, the IL1B promoter, which is inactive in Spi-1-deficient HeLa cells, is activated in these cells by cotransfection with a Spi-1 expression vector. Thus, the cell-type-specific expression of the IL1B promoter appears to be dependent on the binding of Spi-1.

Cement gland-specific activation of the Xag1 promoter is regulated by co-operation of putative Ets and ATF/CREB transcription factors

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4387-4397
Author(s):  
Fiona C. Wardle ◽  
Daniel H. Wainstock ◽  
Hazel L. Sive
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Site ◽  
Reporter Gene ◽  
Binding Sites ◽  
Cement Gland ◽  
Specific Expression ◽  
Necessary And Sufficient ◽  
Do So

The cement gland marks the extreme anterior ectoderm of the Xenopus embryo, and is determined through the overlap of several positional domains. In order to understand how these positional cues activate cement gland differentiation, the promoter of Xag1, a marker of cement gland differentiation, was analyzed. Previous studies have shown that Xag1 expression can be activated by the anterior-specific transcription factor Otx2, but that this activation is indirect. 102 bp of upstream genomic Xag1 sequence restricts reporter gene expression specifically to the cement gland. Within this region, putative binding sites for Ets and ATF/CREB transcription factors are both necessary and sufficient to drive cement gland-specific expression, and cooperate to do so. Furthermore, while the putative ATF/CREB factor is activated by Otx2, a factor acting through the putative Ets-binding site is not. These results suggest that Ets-like and ATF/CREB-like family members play a role in regulating Xag1 expression in the cement gland, through integration of Otx2 dependent and independent pathways.

scholarly journals Absence of Mal/TIRAP Results in Abrogated Imidazoquinolinones-Dependent Activation of IRF7 and Suppressed IFNβ and IFN-I Activated Gene Production

2020 ◽  
Vol 21 (23) ◽  
pp. 8925
Author(s):  
Ewa Leszczyńska ◽  
Edyta Makuch ◽  
Małgorzata Mitkiewicz ◽  
Izabella Jasyk ◽  
Miwako Narita ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factor ◽  
Intracellular Signaling ◽  
Innate Immune ◽  
Signaling Cascades ◽  
Signaling Cascade ◽  
Type I ◽  
Type I Ifns ◽  
Activation Of Transcription ◽  
Intracellular Signaling Molecules

Activation of TLR7 by small imidazoquinoline molecules such as R848 or R837 initiates signaling cascades leading to the activation of transcription factors, such as AP-1, NF-κB, and interferon regulatory factors (IRFs) and afterward to the induction of cytokines and anti-viral Type I IFNs. In general, TLRs mediate these effects by utilizing different intracellular signaling molecules, one of them is Mal. Mal is a protein closely related to the antibacterial response, and its role in the TLR7 pathways remains poorly understood. In this study, we show that Mal determines the expression and secretion of IFNβ following activation of TLR7, a receptor that recognizes ssRNA and imidazoquinolines. Moreover, we observed that R848 induces Mal-dependent IFNβ production via ERK1/2 activation as well as the transcription factor IRF7 activation. Although activation of TLR7 leads to NF-κB-dependent expression of IRF7, this process is independent of Mal. We also demonstrate that secretion of IFNβ regulated by TLR7 and Mal in macrophages and dendritic cells leads to the IP-10 chemokine expression. In conclusion, our data demonstrate that Mal is a critical regulator of the imidazoquinolinones-dependent IFNβ production via ERK1/2/IRF7 signaling cascade which brings us closer to understanding the molecular mechanism’s regulation of innate immune response.

scholarly journals Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

2014 ◽  
Vol 95 (4) ◽  
pp. 968-979 ◽  
Author(s):  
Renée M. van der Sluis ◽  
Ronald Derking ◽  
Seyguerney Breidel ◽  
Dave Speijer ◽  
Ben Berkhout ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Promoter Activity ◽  
Luciferase Reporter ◽  
Replication Capacity ◽  
Type I ◽  
Subtype B ◽  
Negative Effect ◽  
Ltr Promoter ◽  
Hiv 1

HIV-1 transcription depends on cellular transcription factors that bind to sequences in the long-terminal repeat (LTR) promoter. Each HIV-1 subtype has a specific LTR promoter configuration, and minor sequence changes in transcription factor binding sites (TFBSs) or their arrangement can influence transcriptional activity, virus replication and latency properties. Previously, we investigated the proviral latency properties of different HIV-1 subtypes in the SupT1 T cell line. Here, subtype-specific latency and replication properties were studied in primary PHA-activated T lymphocytes. No major differences in latency and replication capacity were measured among the HIV-1 subtypes. Subtype B and AE LTRs were studied in more detail with regard to a putative AP-1 binding site using luciferase reporter constructs. c-Jun, a member of the AP-1 transcription factor family, can activate both subtype B and AE LTRs, but the latter showed a stronger response, reflecting a closer match with the consensus AP-1 binding site. c-Jun overexpression enhanced Tat-mediated transcription of the viral LTR, but in the absence of Tat inhibited basal promoter activity. Thus, c-Jun can exert a positive or negative effect via the AP-1 binding site in the HIV-1 LTR promoter, depending on the presence or absence of Tat.

scholarly journals Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif.

1994 ◽  
Vol 14 (7) ◽  
pp. 4408-4418 ◽  
Author(s):  
K S Moulton ◽  
K Semple ◽  
H Wu ◽  
C K Glass
Keyword(s):  
Gene Family ◽  
Binding Site ◽  
Transcriptional Control ◽  
Transcriptional Start Site ◽  
Receptor Gene ◽  
Regulatory Elements ◽  
Type I ◽  
Start Site ◽  
Macrophage Differentiation ◽  
Ets Domain

The type I and II scavenger receptors (SRs) are highly restricted to cells of monocyte origin and become maximally expressed during the process of monocyte-to-macrophage differentiation. In this report, we present evidence that SR genomic sequences from -245 to +46 bp relative to the major transcriptional start site were sufficient to confer preferential expression of a reporter gene to cells of monocyte and macrophage origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positive transcriptional control was primarily determined by two elements, located 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PU.1/Spi-1, a macrophage and B-cell-specific transcription factor that is a member of the ets domain gene family. Intriguingly, the -181 element represented a relatively low-affinity binding site for Spi-B, a closely related member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These observations support the idea that PU.1/Spi-1 and Spi-B regulate overlapping but nonidentical sets of genes. The -46 element represented a composite binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines and that formed ternary complexes with members of the AP-1 gene family. In concert, these observations suggest a model for how interactions between cell-specific and more generally expressed transcription factors function to dictate the appropriate temporal and cell-specific patterns of SR expression during the process of macrophage differentiation.

Cell-specific expression of the macrophage scavenger receptor gene is dependent on PU.1 and a composite AP-1/ets motif

1994 ◽  
Vol 14 (7) ◽  
pp. 4408-4418
Author(s):  
K S Moulton ◽  
K Semple ◽  
H Wu ◽  
C K Glass
Keyword(s):  
Gene Family ◽  
Binding Site ◽  
Transcriptional Control ◽  
Transcriptional Start Site ◽  
Receptor Gene ◽  
Regulatory Elements ◽  
Type I ◽  
Start Site ◽  
Macrophage Differentiation ◽  
Ets Domain

The type I and II scavenger receptors (SRs) are highly restricted to cells of monocyte origin and become maximally expressed during the process of monocyte-to-macrophage differentiation. In this report, we present evidence that SR genomic sequences from -245 to +46 bp relative to the major transcriptional start site were sufficient to confer preferential expression of a reporter gene to cells of monocyte and macrophage origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positive transcriptional control was primarily determined by two elements, located 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PU.1/Spi-1, a macrophage and B-cell-specific transcription factor that is a member of the ets domain gene family. Intriguingly, the -181 element represented a relatively low-affinity binding site for Spi-B, a closely related member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These observations support the idea that PU.1/Spi-1 and Spi-B regulate overlapping but nonidentical sets of genes. The -46 element represented a composite binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines and that formed ternary complexes with members of the AP-1 gene family. In concert, these observations suggest a model for how interactions between cell-specific and more generally expressed transcription factors function to dictate the appropriate temporal and cell-specific patterns of SR expression during the process of macrophage differentiation.

scholarly journals Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 285-295 ◽  
Author(s):  
Gwonhwa Song ◽  
Fuller W Bazer ◽  
Thomas E Spencer
Keyword(s):  
Immune Cells ◽  
Transcriptional Profiling ◽  
Immune Defense ◽  
Type I ◽  
Uterine Receptivity ◽  
Antiviral Protein ◽  
Interferon Tau ◽  
Independent Manner ◽  
Uterine Endometrium ◽  
A Cell

Radical S-adenosyl methionine domain containing 2 (RSAD2) encodes a cytoplasmic antiviral protein induced by interferons (IFN). Interferon-induced with helicase C domain 1 (IFIH1) is a RNA helicase involved in innate immune defense against viruses, growth suppression, and apoptosis. Interferon tau (IFNT), a Type I IFN produced by the peri-implantation ruminant conceptus, acts on the uterine endometrium to signal pregnancy recognition and promote receptivity to implantation. Transcriptional profiling identifiedRSAD2andIFIH1as IFNT regulated genes in the ovine uterine endometrium. This study tested the hypothesis thatRSAD2andIFIH1were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy. EndometrialRSAD2andIFIH1mRNA increased between days 12 and 16 of pregnancy, but not of the estrous cycle. In pregnant ewes,RSAD2andIFIH1mRNAs increased in endometrial glands, and stroma and immune cells, but not in the luminal epithelium. Neither gene was expressed in the trophectoderm of day 18 or 20 conceptuses. Progesterone (P4) treatment of ovariectomized ewes did not induce expressionRSAD2orIFIH1mRNA in the endometrium; however, intrauterine injections of IFNT induced expression ofRSAD2andIFIH1mRNA in endometria of ewes treated with P4, as well as in ewes treated with P4 and the progesterone receptor antagonist, ZK 136,317. These results indicate that conceptus IFNT induces bothRSAD2andIFIH1in a P4-independent manner in the ovine uterine endometrium. These two IFNT-stimulated genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation through induction of an antiviral state and modulation of local immune cells in the endometrium.

scholarly journals Interferon-tau and fertility in ruminants

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F33-F43 ◽  
Author(s):  
N Forde ◽  
P Lonergan
Keyword(s):  
Prostaglandin F2α ◽  
Threshold Level ◽  
Type I ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Domestic Ruminants ◽  
Oxytocin Receptors ◽  
Pregnancy Recognition ◽  
Maternal Recognition Of Pregnancy ◽  
Primary Agent

Establishment of pregnancy in domestic ruminants includes pregnancy recognition signalling by the conceptus, implantation and placentation. Despite the high fertilisation success rate in ruminants, a significant amount of embryo loss occurs, primarily during early gestation. Interferon-tau (IFNT), a type I interferon that is exclusively secreted by the cells of the trophectoderm of the ruminant conceptus, has been recognised as the primary agent for maternal recognition of pregnancy in ruminants. It produces its antiluteolytic effect on the corpus luteum by inhibiting the expression of oxytocin receptors in the uterine epithelial cells, which prevents pulsatile, luteolytic secretion of prostaglandin F2α by the uterine endometrium. While the importance of IFNT in maternal recognition of pregnancy and prevention of luteolysis in ruminants is unequivocal, important questions, for example, relating to the threshold level of IFNT required for pregnancy maintenance, remain unanswered. This paper reviews data linking IFNT with measures of fertility in ruminants.

scholarly journals The Th1 cell regulatory circuitry is largely conserved between human and mouse

2021 ◽  
Author(s):  
Stephen Henderson ◽  
Venu Pullabhatla ◽  
Arnulf Hertweck ◽  
Emanuele de Rinaldis ◽  
Javier Herrero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Site ◽  
Inflammatory Diseases ◽  
Specific Gene ◽  
Type I ◽  
Th1 Cell ◽  
Specific Expression ◽  
A Genome ◽  
Species Specific

ABSTRACTGene expression programmes controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence due to exposure to species-specific pathogens. T-bet (Tbx21) is the immune-specific lineage-defining transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We therefore compared T-bet genomic targets between mouse and human CD4+ T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we show that the vast majority of T-bet regulated genes are conserved between mouse and human, either via preservation of a binding site or via an alternative binding site associated with transposon-linked insertion. We also identified genes that are specifically targeted by T-bet in humans or mice and which exhibited species-specific expression. These results provide a genome-wide cross-species comparison of T-bet target gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory disease into human clinical trials.

Sign in / Sign up

Export Citation Format

Share Document