Pattern formation in the limbs of Drosophila: bric a brac is expressed in both a gradient and a wave-like pattern and is required for specification and proper segmentation of the tarsus

Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 799-812 ◽  
Author(s):  
D. Godt ◽  
J.L. Couderc ◽  
S.E. Cramton ◽  
F.A. Laski
Keyword(s):  
Transcription Factors ◽  
Pattern Formation ◽  
Expression Pattern ◽  
Nuclear Protein ◽  
Tarsal Segment ◽  
Conserved Domain ◽  
Bristle Pattern

We have identified the gene bric a brac and show that it is required for pattern formation along the proximal-distal axis of the leg and antenna of Drosophila. In bric a brac mutant legs, the bristle pattern of the three central tarsal segments is transformed towards the pattern of the most proximal tarsal segment. In addition, bric a brac mutant legs and antennae have segmentation defects. bric a brac encodes a nuclear protein that shares a highly conserved domain with two transcription factors from Drosophila. bric a brac function is dosage dependent and is required in a graded manner for the specification of tarsal segments. The graded requirement for bric a brac correlates with its graded expression pattern, suggesting that the concentration of BRIC A BRAC protein specifies segment identity in the tarsus.

Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors

1994 ◽  
Vol 14 (2) ◽  
pp. 1153-1159
Author(s):  
C Y Wang ◽  
A G Bassuk ◽  
L H Boise ◽  
C B Thompson ◽  
R Bravo ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nuclear Protein ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Transcriptional Induction

The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation. The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor. A highly conserved 19-bp element located immediately 5' of the human GM-CSF TATA box (bp -34 to -52), herein called purine box 1 (PB1), has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation. The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes. In this report, we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells. In addition, we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation. Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors. In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells. Using antibodies specific for different Ets and AP-1 family members, we demonstrate that the major inducible PB1-binding activity present in activated T-cell nuclear extracts is composed of the Elf-1, c-Fos, and JunB transcription factors. Taken together, these results suggest that cooperative interactions between specific Ets and AP-1 family members are important in regulating inducible gene expression following T-cell activation.

scholarly journals Expression pattern of dd4, a sole member of the d4 family of transcription factors in Drosophila melanogaster

2002 ◽  
Vol 114 (1-2) ◽  
pp. 119-123 ◽  
Author(s):  
Elena Nabirochkina ◽  
Olga B. Simonova ◽  
Ilja B. Mertsalov ◽  
Dina A. Kulikova ◽  
Nadezshda G. Ladigina ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Factors ◽  
Expression Pattern

178 Cellular and extracellular expression of stress response transcription factors in male and female bovine pre-implantation embryos under oxidative stress conditions

2019 ◽  
Vol 31 (1) ◽  
pp. 213
Author(s):  
M. O. Taqi ◽  
S. Gebremedhn ◽  
D. Salilew-Wondim ◽  
F. Rings ◽  
C. Neuhoff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Cell Count ◽  
Expression Pattern ◽  
Total Cell ◽  
Expression Level ◽  
Total Cell Count ◽  
Oxygen Level ◽  
Male And Female

Pre-implantation embryo development is a critical stage, in which several development and stress-response related transcription factors (TF) are involved. Exposing embryos to environmental insults alter some of these stress response-related TF. However, their expression pattern in male and female embryos and their release via exosomes is still unclear. Here, we aimed to investigate the effect of culture-induced oxidative stress on development and expression pattern of stress-related TF in male and female embryos and in respective spent media coupled with exosomes. For this, bovine male and female zygotes were in vitro produced using sexed semen and cultured under 5% and 20% oxygen in exosome-depleted SOFaa medium (SOF with amino acids). Blastocysts were subjected to total RNA isolation followed by quantitative RT-PCR analysis of the selected TF (Nrf2, KLF4, NOTCH1, SREBF2, E2F1, CAT1, SOD1, and OCT4), as well as protein abundance analysis using immunofluorescence and related phenotypes analysis, including reactive oxygen species (ROS) level and total cell count. Furthermore, the spent embryo culture media were collected for exosomes isolation and expression analysis of candidate TF. The data were statistically analysed using one-way ANOVA followed by multiple pair-wise comparisons using the Tukey post hoc test. Results showed that the blastocyst rates of both male (29.9% v. 34.9%) and female (16.7% v. 26.5%) bovine embryos were significantly lower in 20% than in 5% oxygen level. Female blastocysts subjected to the higher oxygen level showed increased ROS level (37.66±1.70v. 45.32±2.05 in male and 29.42±1.44v. 45.51±2.06 in female) and significantly reduced total cell count compared with the male embryo counterpart (136.55±7.8v. 112.75±2.9 in male and 138.75±2.0v. 88.25±4.3 in female cultured in 5% and 20% oxygen levels, respectively). Consequently, the expression levels of Nrf2, KLF4, SREBF2, CAT1, SOD1, and OCT4 were significantly increased in male embryos exposed to oxidative stress compared with those cultured under the lower oxygen level. However, NOTCH1 and E2F1 were significantly increased in female embryos exposed to oxidative stress compared with the male counterparts. The mRNA level of SREBF2 was significantly increased in male embryos cultured under both 5% and 20% O2 compared with female embryos. The protein expression level of Nrf2 and KLF4 was higher in embryos cultured at 20% v. 5% O2 with greater Nrf2 abundance in male embryos. Consequently, the male embryos produced at 20% O2 released a higher number of exosomes enriched with Nrf2, SOD1, and NOTCH1 mRNA than the other groups. Interestingly, the exosomal mRNA expression level of E2F1 tended to be higher in female embryos exposed to oxidative stress than their male counterparts. Taken together, the male embryos were more tolerant to oxidative stress than female embryos via the activation Nrf2-mediated oxidative stress response and development related TF. The release of these TF via exosomes could enhance cellular homeostasis maintenance under oxidative stress.

scholarly journals Ubinuclein, a Novel Nuclear Protein Interacting with Cellular and Viral Transcription Factors

2000 ◽  
Vol 148 (6) ◽  
pp. 1165-1176 ◽  
Author(s):  
Sirpa Aho ◽  
Monique Buisson ◽  
Tiina Pajunen ◽  
Young W. Ryoo ◽  
Jean-Francois Giot ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Leucine Zipper ◽  
Nuclear Protein ◽  
Cellular Protein ◽  
Early Gene ◽  
Nuclear Staining ◽  
Basic Leucine Zipper ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

The major target tissues for Epstein-Barr virus (EBV) infection are B lymphocytes and epithelial cells of the oropharyngeal zone. The product of the EBV BZLF1 early gene, EB1, a member of the basic leucine-zipper family of transcription factors, interacts with both viral and cellular promoters and transcription factors, modulating the reactivation of latent EBV infection. Here, we characterize a novel cellular protein interacting with the basic domains of EB1 and c-Jun, and competing of their binding to the AP1 consensus site. The transcript is present in a wide variety of human adult, fetal, and tumor tissues, and the protein is detected in the nuclei throughout the human epidermis and as either grainy or punctuate nuclear staining in the cultured keratinocytes. The overexpression of tagged cDNA constructs in keratinocytes revealed that the NH2 terminus is essential for the nuclear localization, while the central domain is responsible for the interaction with EB1 and for the phenotype of transfected keratinocytes similar to terminal differentiation. The gene was identified in tail-to-tail orientation with the periplakin gene (PPL) in human chromosome 16p13.3 and in a syntenic region in mouse chromosome 16. We designated this novel ubiquitously expressed nuclear protein as ubinuclein and the corresponding gene as UBN1.

scholarly journals Molecular regulation of the human IL-3 gene: inducible T cell-restricted expression requires intact AP-1 and Elf-1 nuclear protein binding sites.

1993 ◽  
Vol 178 (5) ◽  
pp. 1681-1692 ◽  
Author(s):  
L R Gottschalk ◽  
D M Giannola ◽  
S G Emerson
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Protein Binding ◽  
Binding Site ◽  
Binding Sites ◽  
Nuclear Protein ◽  
Mobility Shift ◽  
Nuclear Extracts ◽  
Mobility Shift Assay

Interleukin 3 (IL-3) is a hematopoietic stem-cell growth and differentiation factor that is expressed solely in activated T and NK cells. Studies to date have identified elements 5' to the IL-3 coding sequences that regulate its transcription, but the sequences that confer T cell-specific expression remain to be clearly defined. We have now identified DNA sequences that are required for T cell-restricted IL-3 gene transcription. A series of transient transfections performed with human IL-3-chloramphenicol acetyltransferase (CAT) reporter plasmids in T and non-T cells revealed that a plasmid containing 319 bp of 5' flanking sequences was active exclusively in T cells. Deletion analysis revealed that T cell specificity was conferred by a 49-bp fragment (bp -319 to -270) that included a potential binding site for AP-1 transcription factors 6 bp upstream of a binding site for Elf-1, a member of the Ets family of transcription factors. DNaseI footprint and electrophoretic mobility shift assay analyses performed with MLA-144 T cell nuclear extracts demonstrated that this 49-bp region contains a nuclear protein binding region that includes consensus AP-1 and Elf-1 binding sites. In addition, extracts prepared from purified human T cells contained proteins that bound to synthetic oligonucleotides corresponding to the AP-1 and Elf-1 binding sites. In vitro-transcribed and -translated Elf-1 protein bound specifically to the Elf-1 site, and Elf-1 antisera competed and super shifted nuclear protein complexes present in MLA-144 nuclear extracts. Moreover, addition of anti-Jun family antiserum in electrophoretic mobility shift assay reactions completely blocked formation of the AP-1-related complexes. Transient transfection studies in MLA-144 T cells revealed that constructs containing mutations in the AP-1 site almost completely abolished CAT activity while mutation of the Elf-1 site or the NF-IL-3 site, a previously described nuclear protein binding site (bp. -155 to -148) in the IL-3 promoter, reduced CAT activity to < 25% of the activity given by wild-type constructs. We conclude that expression of the human IL-3 gene requires the AP-1 and Elf-1 binding sites; however, unlike other previously characterized cytokine genes such as IL-2, the AP-1 and Elf-1 factors can bind independently in the IL-3 gene.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Exploring the Expression Profile of Long Non-Coding RNA (lncRNA) in Different Acute Myeloid Leukemia (AML) Subtypes: t(8;16)(p11;p13)/MYST3-Crebbp AML Harbors a Distinctive Lncrna Signature

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1397-1397 ◽  
Author(s):  
Marina Diaz-Beya ◽  
Alfons Navarro ◽  
Anna Cordeiro ◽  
Marta Pratcorona ◽  
Joan Castellano ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Transcription Factors ◽  
Expression Pattern ◽  
Expression Profile ◽  
Myeloid Leukemia ◽  
Genomic Region ◽  
Differentially Expressed ◽  
Specific Gene ◽  
Lncrna Expression ◽  
Acute Myeloid

Abstract Introduction: Long non-coding RNAs (lncRNAs) have recently emerged as important actors in the regulation of multiple cellular processes including cancer. Acute myeloid leukemia (AML) is a heterogeneous disease; most of the main cytogenetic AML subgroups harbor a specific gene expression profile. AML with translocation t(8;16)(p11;p13) (t(8;16) AML) is a subtype with specific clinical and biological characteristics including a distinctive gene (Camós et al, Cancer Research 2006) and microRNA (Díaz-Beyá et al, Leukemia 2013) expression profile. In this translocation, MYST3 on chromosome 8p11 fuses with CREBBP on chromosome 16p13.3. The MYST3-CREBBP fusion protein is able to interact with multiple transcription factors (TF) producing a disturbed transcriptional program. However, the lncRNA expression pattern of different cytogenetic AML subtypes, including t(8;16) AML, have not been described yet. Aims: To examine the expression profile of lncRNAs within different AML subtypes, and to characterize the expression pattern of lncRNAs in t(8;16) AML in comparison to other AML subtypes. Patients and Methods: 46 AML patients, 4 normal bone marrow (NBM) and 3 CD34+ NBM samples were included in the study. Samples included different AML subtypes: intermediate-risk cytogenetic AML (IR-AML, n=18), t(15;17) (APL, n=4), t(8;21) AML (n=4), inv(16) AML(n=2), t(6;9) AML (n=7), AML with monosomal karyotype (n=4), t(3;3) AML (n=1), t(9;11) AML (n=1) and t(8;16) AML (n=5). Within IR-AML patients with a different mutational profile: FLT3-ITD (n=7), NPM1 (n=5), CEBPA (n=7) and DNMT3A (n=6) were included. The lncRNA expression was studied using Affymetrix® Human Gene 2.1 ST platform which includes 9698 lncRNAs transcripts. The filtering and normalization of the array data was performed using oligo package from Bioconductor. Statistical analyses were performed with TiGR MultiExperiment Viewer, BRB tools and R. The Transcription factor Affinity Prediction Web Tool was used to determine the putative transcription factors binding to the differentially expressed lncRNAs promoters. Results: The hierarchical cluster analysis showed that all 4 NBM as well as all 3 CD34+ NBM clustered together according to their lncRNA expression. Interestingly, all 5 t(8;16) AML samples clustered together, as well as the 3 APL, the 7 t(6;9) AML and 5 out of 7 cases with CEBPA mutations. The specific lncRNA signature of APL was composed of 79 differentially expressed lncRNA and t(6;9) AML lncRNA signature comprised of 15 differentially expressed lncRNAs. When we focused on t(8;16) AML lncRNA profile, we identified an specific 113-lncRNA signature in the supervised analysis (Figure). Interestingly, when we analyzed which (TF) had motifs overrepresented in the promoters regions of the t(8;16) AML lncRNA signature, we identified GATA2 as the TF with significantly overrepresented motifs for GATA2 (p<0.001). Interestingly, levels of GATA2 were differentially expressed in t(8;16) AML samples in comparison with other AMLs samples (p<0.001). GATA2 has been described to interact with CREBBP, one of the partners involved in t(8;16) AML. Of note, 4 overexpressed lncRNAs of the signature (linc-HOXA11, HOXA11-AS, HOTTIP and NR_038120) were located in the HOXA genomic region, previously found upregulated in t(8:16) AML. Since several studies suggest an active crosstalk between microRNAs and lncRNAs, we also correlated the expression of these lncRNAs with the microRNA t(8;16) AML profile. We found significant correlation between linc-HOXA11 and miR-222* (R2 =0.996, p=0.003), HOXA11-AS and miR-let-7c (R2=0.994, p=0.006), HOTTIP and miR-196b*(R2=0.958, p=0.041), and NR_038120 with miR-486-3p (R2=0.999, p=0.0004) and miR-19a (R2=0.953, p=0.04). Conclusions: LncRNAs expression profile seems specific of several AML subtypes, including t(8;16) AML. Some of the lncRNAs of this distinctive signature in t(8;16) AML are located in the HOXA genomic region, and correlate with several of the characteristic microRNAs previously described in this entity. Interestingly, we have predicted in silico GATA2, which interacts with CREBBP, as the most significant TF that could potentially regulate this lncRNAs signature. Nonetheless, further investigation is warranted to determine the mechanisms leading to this lncRNA signature and to identify the specific targets of these lncRNAs. Río Hortega CM13/00205, FIS PI13/00999 Disclosures No relevant conflicts of interest to declare.

Immunohistochemical Analysis of the Expression of the B- Cell Markers BCL-6, MUM1/IRF4, CD79A and Transcription Factors BOB.1 and OCT.2 in Classical Hodgkin Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 974-974
Author(s):  
S. Valsami ◽  
D. Rontogianni ◽  
V. Pappa ◽  
T. Economopoulos ◽  
F. Kontsioti ◽  
...  
Keyword(s):  
Transcription Factors ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Expression Pattern ◽  
Disease Free Survival ◽  
Classical Hodgkin Lymphoma ◽  
Time To Progression ◽  
Free Survival ◽  
Cell Markers ◽  
Disease Free

Abstract INTRODUCTION: Classical hodgkin’s lymphoma can be considered in most cases as a B-cell lymphoma by the presence of potentially functional immunoglobulin gene rearrangements in Hodgkin/Reed Sternberg (H-RS) cells However the expression of B cell markers in classical Hodgkin lymphoma is rare and the light and heavy chain mRNA is lacking. The exact mechanism for this discrepancy is not known, and some studies have suggested a transcription machinery deficiency. The aim of our study was the detection of B cell markers like CD79a, bcl6 and MUM.1/IRF4 in relation to B cell transcription factors BOB.1 and OCT.2 in classical Hodgkin lymphoma in order to define subgroups with different histogenesis and prognosis. Patients and methods: The analysis included 107 cases of classical Hodgkin lymphoma 55 males and 52 females with a median age of 37 (13–79). They were staged as: 17 stage I, 55 stage II, 13 stage III and 22 stage IV. Advanced stage patients were risk stratified according to the IPI, and early according to EORTC. The histological subtype was: Nodular sclerosis 76, Mixed cellularity 19, Lymphocyte depleted 5 and lymphocyte rich 7 cases. Extranodal disease was present in 24/107 (22.4%) cases. Diagnostic biopsies were used for histochemical detection of bcl/6, CD79a, MUM-IRF4 and B cell transcription factors BOB.1, OCT.2. Expression was considered as low if detected in 1–25%, medium in 26–49% and high in &gt; 50% of H/RS cells. RESULTS Bcl6 was expressed in 22/101 cases, MUM.1 in 81/107 cases, BOB.1 in 89/100, OCT.2 in 17/100 and CD79a in 6/101 cases. In positive cases, bcl6, CD79a and OCT.2 have shown low expression, while MUM.1 and BOB.1 had a high expression in the majority of cases. There was not any difference in the expression pattern between different histologic subtypes for all these markers. Bcl6, MUM.1, OCT.2 and CD79a expression were not significantly different for different risk group categories and did not influence overall survival, disease free survival or time to progression. Cases positive for MUM expression had a significantly lower Hb (p=0.03), lower albumin (p=0.02), and higher IgG value (p=0.01). BOB.1 was expressed in 25% of early favourable, in 35% of intermediate and 40% of unfavourable early stage disease (p=0.06).There was a positive correlation between B symptoms and BOB.1 expression (p=0.01). There was a positive correlation between the expression of bcl6 and OCT.2 and between OCT.2 and CD79a (p=0.05, p=0.01) respectively. CONCLUSION MUM is expressed in the majority of classical Hodgkin lymphoma cases confirming its histogenesis from a late centrocyte and post/germinal centre B cell. B cell markers and transcription factors were not significant for survival, disease free survival and time to progression and their expression pattern was not different between different histological subtypes and risk groups of classical Hodgkin lymphoma.

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