scholarly journals Activation of Somatostatin Receptor II Expression by Transcription Factors MIBP1 and SEF-2 in the Murine Brain

1999 ◽  
Vol 19 (5) ◽  
pp. 3736-3747 ◽  
Author(s):  
Ulrike Dörflinger ◽  
Armin Pscherer ◽  
Markus Moser ◽  
Petra Rümmele ◽  
Roland Schüle ◽  
...  

ABSTRACT Somatostatin receptor type II expression in the mammalian brain displays a spatially and temporally very restricted pattern. In an investigation of the molecular mechanisms controlling these patterns, we have recently shown that binding of the transcription factor SEF-2 to a novel initiator element in the SSTR-2 promoter is essential for SSTR-2 gene expression. Further characterization of the promoter identified a species-conserved TC-rich enhancer element. By screening a mouse brain cDNA expression library, we cloned a cDNA encoding the transcription factor MIBP1. MIBP1 interacts specifically with both the TC box in the SSTR-2 promoter and with the SEF-2 initiator-binding protein to enhance transcription from the basal SSTR-2 promoter. We then investigated SSTR-2, SEF-2, and MIBP1 mRNA expression patterns in the developing and adult murine brain by Northern blotting and in situ hybridization. While SEF-2 is widely expressed in many neuronal and nonneuronal tissues, MIBP1 expression overlapped precisely with expression of SSTR-2 in the frontal cortex and hippocampus. In summary, our data for the first time define a regulatory role for the transcription factor MIBP1 in mediating spatially and temporally regulated SSTR-2 expression in the brain.

Development ◽  
1991 ◽  
Vol 111 (2) ◽  
pp. 497-507 ◽  
Author(s):  
P. Ferretti ◽  
J.P. Brockes ◽  
R. Brown

In order to understand the molecular mechanisms underlying the regenerative ability of the urodele limb, it is important to identify regeneration-associated proteins and to study their regulation. We have recently shown that the anti-cytokeratin monoclonal antibody LP1K reacts strongly with newt blastemal cells, while its reactivity is restricted in normal limbs. By screening a cDNA expression library from the newt blastema with LP1K, we have identified cDNA clones coding for a type II keratin (NvKII) expressed both in the mesenchyme and the specialized wound epithelium of the blastema. While the rod domain of the protein is highly conserved, the homology between NvKII and mammalian type II keratins drops markedly at the N- and C-terminal regions. The expression of this keratin was analysed by Northern blotting and RNAase protection analysis of various newt tissues, and appears to be organ specific, since it is restricted to normal and regenerating limbs and tails. In particular, we have investigated the expression of this keratin mRNA in normal and regenerating limbs. The transcript is barely detectable in the proximal portion of the normal limb, but its level is high in the distal one. After amputation, NvKII mRNA is expressed both in proximal and distal blastemas, although at higher levels distally, indicating that this keratin is regeneration associated. The NvKII transcript is detectable both in mesenchyme and in the wound epithelium of the regenerate, while no transcript is detectable in normal epidermis. The level of NvKII mRNA is markedly down-regulated both in normal and regenerating limbs following intraperitoneal injection with retinoic acid, a putative endogenous morphogen in limb regeneration.


1991 ◽  
Vol 11 (10) ◽  
pp. 4863-4875
Author(s):  
S V Iyer ◽  
D L Davis ◽  
S N Seal ◽  
J B Burch

We screened a chicken liver cDNA expression library with a probe spanning the distal region of the chicken vitellogenin II (VTGII) gene promoter and isolated clones for a transcription factor that we have named VBP (for vitellogenin gene-binding protein). VBP binds to one of the most important positive elements in the VTGII promoter and appears to play a pivotal role in the estrogen-dependent regulation of this gene. The protein sequence of VBP was deduced from a nearly full length cDNA copy and was found to contain a basic/zipper (bZIP) motif. As expected for a bZIP factor, VBP binds to its target DNA site as a dimer. Moreover, VBP is a stable dimer free in solution. A data base search revealed that VBP is related to rat DBP. However, despite the fact that the basic/hinge regions of VBP and DBP differ at only three amino acid positions, the DBP binding site in the rat albumin promoter is a relatively poor binding site for VBP. Thus, the optimal binding sites for VBP and DBP may be distinct. Similarities between the VBP and DBP leucine zippers are largely confined to only four of the seven helical spokes. Nevertheless, these leucine zippers are functionally compatible and appear to define a novel subfamily. In contrast to the bZIP regions, other portions of VBP and DBP are markedly different, as are the expression profiles for these two genes. In particular, expression of the VBP gene commences early in liver ontogeny and is not subject to circadian control.


2000 ◽  
Vol 150 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Masahiro Iwamoto ◽  
Yoshinobu Higuchi ◽  
Eiki Koyama ◽  
Motomi Enomoto-Iwamoto ◽  
Kojiro Kurisu ◽  
...  

During limb development, chondrocytes located at the epiphyseal tip of long bone models give rise to articular tissue, whereas the more numerous chondrocytes in the shaft undergo maturation, hypertrophy, and mineralization and are replaced by bone cells. It is not understood how chondrocytes follow these alternative pathways to distinct fates and functions. In this study we describe the cloning of C-1-1, a novel variant of the ets transcription factor ch-ERG. C-1-1 lacks a short 27–amino acid segment located ∼80 amino acids upstream of the ets DNA binding domain. We found that in chick embryo long bone anlagen, C-1-1 expression characterizes developing articular chondrocytes, whereas ch-ERG expression is particularly prominent in prehypertrophic chondrocytes in the growth plate. To analyze the function of C-1-1 and ch-ERG, viral vectors were used to constitutively express each factor in developing chick leg buds and cultured chondrocytes. We found that virally driven expression of C-1-1 maintained chondrocytes in a stable and immature phenotype, blocked their maturation into hypertrophic cells, and prevented the replacement of cartilage with bone. It also induced synthesis of tenascin-C, an extracellular matrix protein that is a unique product of developing articular chondrocytes. In contrast, virally driven expression of ch-ERG significantly stimulated chondrocyte maturation in culture, as indicated by increases in alkaline phosphatase activity and deposition of a mineralized matrix; however, it had modest effects in vivo. The data show that C-1-1 and ch-ERG have diverse biological properties and distinct expression patterns during skeletogenesis, and are part of molecular mechanisms by which limb chondrocytes follow alternative developmental pathways. C-1-1 is the first transcription factor identified to date that appears to be instrumental in the genesis and function of epiphyseal articular chondrocytes.


2020 ◽  
Author(s):  
Yufei Xiao ◽  
Junji Li ◽  
Ye Zhang ◽  
Xiaoning Zhang ◽  
Hailong Liu ◽  
...  

Abstract Background: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE.Results: We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus species – E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). Initially, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9,229 and 8,989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively, and 2,687 up-regulated and 2,581 down-regulated genes shared. Next, we identified 2,003 up-regulated and 1,958 down-regulated genes only in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone, 122 cell wall related and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in the dedifferentiation process of E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4,723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla. Conclusions: This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. It will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yufei Xiao ◽  
Junji Li ◽  
Ye Zhang ◽  
Xiaoning Zhang ◽  
Hailong Liu ◽  
...  

Abstract Background Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE. Results We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus species – E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). Initially, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9229 and 8989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively, and 2687 up-regulated and 2581 down-regulated genes shared. Next, we identified 2003 up-regulated and 1958 down-regulated genes only in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone, 122 cell wall related and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in the dedifferentiation process of E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla. Conclusions This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. It will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.


2022 ◽  
Author(s):  
Anna Duenser ◽  
Pooja Singh ◽  
Laurene Alicia Lecaudey ◽  
Christian Sturmbauer ◽  
Craig Albertson ◽  
...  

Studying instances of convergent evolution of novel phenotypes can shed light on the evolutionary constraints that shape morphological diversity. Cichlid fishes from the East African Great Lakes are a prime model to investigate convergent adaptations. However, most studies on cichlid craniofacial morphologies have primarily considered bony structures, while soft tissue adaptations have been less intensely scrutinised. A rare example of an exaggerated soft tissue phenotype is the formation of a snout flap. This tissue flap develops from the upper lip and has evolved in only one cichlid genus from Lake Malawi and one genus from Lake Tanganyika. To investigate the molecular basis of snout flap convergence, we used mRNA sequencing to compare two species with snout flap (Labeotropheus trewavasae and Ophthalmotilapia nasuta) to their close relatives without snout flaps (Tropheops tropheops and Ophthalmotilapia ventralis) from Lake Tanganyika and Malawi. Our analysis revealed a greater complexity of differential gene expression patterns underlying the snout flap in the younger adaptive radiation of Lake Malawi than in the older Lake Tanganyika radiation. We identified 201 genes that were repeatedly differentially expressed between species with and without the snout flap in both lakes, suggesting that the pathway that gives rise to snout flaps is evolutionarily constrained, even though the flaps play very different functions in each species. The convergently expressed genes are involved in proline and hydroxyproline metabolism, which have been linked to human skin and facial deformities. Additionally, we also found enrichment for transcription factor binding sites upstream of differentially expressed genes such as members of the FOX transcription factor family, especially foxf1 and foxa2, which also showed an increased expression in the flapped snout and are linked to nose morphogenesis in mammals, as well as ap4 (tfap4), a transcription factor showing reduced expression in the flapped snout with an unknown role in the development of craniofacial soft tissues. As genes involved in cichlids snout flap development are associated with many human mid-line facial dysmorphologies, our findings imply a conservation of genes involved in mid-line patterning across vastly distant evolutionary lineages of vertebrates.


Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1663
Author(s):  
Thomas Gross ◽  
Annette Becker

Angiosperm flowers are the most complex organs that plants generate, and in their center, the gynoecium forms, assuring sexual reproduction. Gynoecium development requires tight regulation of developmental regulators across time and tissues. How simple on and off regulation of gene expression is achieved in plants was described previously, but molecular mechanisms generating complex expression patterns remain unclear. We use the gynoecium developmental regulator CRABS CLAW (CRC) to study factors contributing to its sophisticated expression pattern. We combine in silico promoter analyses, global TF-DNA interaction screens, and mutant analyses. We find that miRNA action, DNA methylation, and chromatin remodeling do not contribute substantially to CRC regulation. However, 119 TFs, including SEP3, ETT, CAL, FUL, NGA2, and JAG bind to the CRC promoter in yeast. These TFs finetune transcript abundance as homodimers by transcriptional activation. Interestingly, temporal–spatial aspects of expression regulation may be under the control of redundantly acting genes and require higher order complex formation at TF binding sites. Our work shows that endogenous regulation of complex expression pattern requires orchestrated transcription factor action on several conserved promotor sites covering almost 4 kb in length. Our results highlight the utility of comprehensive regulators screens directly linking transcriptional regulators with their targets.


2012 ◽  
Vol 166 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Casey Jo Anne Smith ◽  
Sophie Bensing ◽  
Christine Burns ◽  
Phillip J Robinson ◽  
Anna A Kasperlik-Zaluska ◽  
...  

BackgroundLymphocytic hypophysitis is an organ-specific autoimmune disease of the pituitary gland. A specific and sensitive serological test currently does not exist to aid in the diagnosis.ObjectiveTo identify target autoantigens in lymphocytic hypophysitis and develop a diagnostic assay for these proteins.Design/methodsA pituitary cDNA expression library was immunoscreened using sera from four patients with lymphocytic hypophysitis. Relevant cDNA clones from screening, along with previously identified autoantigens pituitary gland-specific factor 1a and 2 (PGSF1a and PGSF2) and neuron-specific enolase (NSE) were tested in anin vitrotranscription and translation immunoprecipitation assay. The corticotroph-specific transcription factor, TPIT, was investigated separately as a candidate autoantigen.ResultsSignificantly positive autoantibody reactivity against TPIT was found in 9/86 hypophysitis patients vs 1/90 controls (P=0.018). The reactivity against TPIT was not specific for lymphocytic hypophysitis with autoantibodies detectable in the sera from patients with other autoimmune endocrine diseases. Autoantibodies were also detected against chromodomain-helicase-DNA binding protein 8, presynaptic cytomatrix protein (piccolo), Ca2+-dependent secretion activator, PGSF2 and NSE in serum samples from patients with lymphocytic hypophysitis, but at a frequency that did not differ from healthy controls. Importantly, 8/86 patients with lymphocytic hypophysitis had autoantibodies against any two autoantigens in comparison with 0/90 controls (P=0.0093).ConclusionsTPIT, a corticotroph-specific transcription factor, was identified as a target autoantigen in 10.5% of patients with lymphocytic hypophysitis. Further autoantigens related to vesicle processing were also identified as potential autoantigens with different immunoreactivity patterns in patients and controls.


2020 ◽  
Author(s):  
Yufei Xiao ◽  
Junji Li ◽  
Ye Zhang ◽  
Xiaoning Zhang ◽  
Hailong Liu ◽  
...  

Abstract Background: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood due to its increasing importance for fiber and energy in the word. Somatic embryogenesis is one method to provide large-scale commercial use for the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the SE of Eucalyptus on transcriptional level.Results: We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus cultivars – E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). In total, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9,229 and 8,989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively. Comparison of DEGs showed that they shared 2,687 up-regulated and 2,581 down-regulated genes. Next, we found 2,003 up-regulated and 1,958 down-regulated genes specifically identified in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4,723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla. Conclusions: This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. Our results will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.


1995 ◽  
Vol 15 (6) ◽  
pp. 3164-3170 ◽  
Author(s):  
L Sanz ◽  
J Moscat ◽  
M T Diaz-Meco

Stromelysins, which are the metalloproteinases with the widest substrate specificities, play a critical role in tumor invasion and metastasis. We have previously reported an element (SPRE) of the stromelysin promoter located between nucleotides -1221 and -1203 that is necessary and sufficient for the control of stromelysin gene expression by mitogenic activation, which induces a nuclear activity that binds to this sequence. Using a concatenated probe with several copies of this element to screen a lambda gt11 cDNA expression library from mouse Swiss 3T3 fibroblasts, we report here the molecular cloning of a cDNA coding for a novel protein (SPBP) of 937 amino acids that binds to this element and has several features of a transcription factor, such as a putative leucine zipper region, a nuclear localization signal, and a basic domain with homology to the DNA-binding domains of Fos and Jun. Evidence that SPBP is at least a critical component of the mitogen-induced SPRE nuclear binding activity is presented here. Furthermore, the transfection of an expression plasmid for SPBP transactivates reporter chloramphenicol acetyltransferase plasmids containing either the full-length stromelysin promoter or a single copy of the SPRE cloned upstream of the herpes simplex virus thymidine kinase minimal promoter. Therefore, the results presented here identify a novel transcription factor critically involved in the control of stromelysin expression.


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