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At least 73 records · Page 4Linked to original sources
PubMed1992

POU-specific domain of Oct-2 factor confers 'octamer' motif DNA binding specificity on heterologous Antennapedia homeodomain.

The bipartite DNA binding domain of the POU family of transcription factors contains a 'POU-specific' domain unique to this class of factors and a 'POU homeodomain' homologous to other homeodomains. We compared DNA binding of the Oct-2 factor POU domain and the Antennapedia (Antp) homeodomain with a chimeric Oct-2/Antp protein in which the distantly related Antp homeodomain was substituted for the Oct-2 POU homeodomain. The Oct-2/Antp chimeric protein bound both the octamer and the Antp sites efficiently, indicating that DNA binding specificity is contributed by both components of the POU domain.

Antennapedia Homeodomain Protein↗
PubMed1999

Regulation of NGFI-A (Egr-1) gene expression by the POU domain transcription factor Brn-3a.

NGFI-A is an immediate early gene (IEG) that is transcriptionally induced by nerve growth factor (NGF) in PC12 cells and has been implicated in a number of cellular responses. Studies have shown that elements within the first 106 base pairs of the NGFI-A promoter contribute to its induction by NGF in PC12 cells. One element, within the serum response element (SRE) bridge region, bears strong homology to a motif previously identified in promoters regulated by the Brn-3a POU domain transcription factor. We report here that Brn-3a activates the NGFI-A promoter in neurons (both primary and cell lines). Analysis revealed that this response requires sequences between positions -49 and -106. Whilst DNA-protein interaction studies failed to identify a site bound directly by Brn-3a, the data presented here suggest that Brn-3a may cooperate in the regulation of NGFI-A gene expression in neurons, possibly during the developmental switch between neurotrophin dependency that occurs during neurogenesis.

3T3 Cells↗
PubMed2000

The POU domain transcription factor Tst-1 activates somatostatin receptor 1 gene expression in pancreatic beta -cells.

The peptide hormone somatostatin inhibits the release of insulin. The gene encoding somatostatin receptor 1 is expressed in pancreatic beta-cells and insulinoma RIN 1046-38 cells. In the present study the mechanisms underlying the regulation of the somatostatin receptor 1 gene in pancreatic beta-cells were investigated. Transient transfections of RIN 1046-38 cells with promoter/reporter gene constructs and footprint analysis revealed two regions, fp1 and fp2, that were necessary for the observed promoter activity. Mutagenesis of the fp2 region delineated the cis-acting element to the motif 5'-TTAATCATT-3'. The POU domain transcription factor Tst-1 was identified as trans-activator mediating the 5'-TTAATCATT-3' motif-dependent transcription in RIN 1046-38 cells and heterologous CV1 cells. Tst-1, known as a transcriptional regulator in keratinocytes, glial cells, and neurons, has been detected by immunohistochemistry in pancreatic islets. Altogether, we demonstrate Tst-1 as transcriptional regulator in pancreatic neuroendocrine cells.

Animals↗
PubMed2000

Restricted patterning of vestigial expression in Drosophila wing imaginal discs requires synergistic activation by both Mad and the drifter POU domain transcription factor.

The Drosophila Vestigial protein has been shown to play an essential role in the regulation of cell proliferation and differentiation within the developing wing imaginal disc. Cell-specific expression of vg is controlled by two separate transcriptional enhancers. The boundary enhancer controls expression in cells near the dorsoventral (DV) boundary and is regulated by the Notch signal transduction pathway, while the quadrant enhancer responds to the Decapentaplegic and Wingless morphogen gradients emanating from cells near the anteroposterior (AP) and DV boundaries, respectively. MAD-dependent activation of the vestigial quadrant enhancer results in broad expression throughout the wing pouch but is excluded from cells near the DV boundary. This has previously been thought to be due to direct repression by a signal from the DV boundary; however, we show that this exclusion of quadrant enhancer-dependent expression from the DV boundary is due to the absence of an additional essential activator in those cells. The Drosophila POU domain transcriptional regulator, Drifter, is expressed in all cells within the wing pouch expressing a vgQ-lacZ transgene and is also excluded from the DV boundary. Viable drifter hypomorphic mutations cause defects in cell proliferation and wing vein patterning correlated with decreased quadrant enhancer-dependent expression. Drifter misexpression at the DV boundary using the GAL4/UAS system causes ectopic outgrowths at the distal wing tip due to induction of aberrant Vestigial expression, while a dominant-negative Drifter isoform represses expression of vgQ-lacZ and causes severe notching of the adult wing. In addition, we have identified an essential evolutionarily conserved sequence element bound by the Drifter protein with high affinity and located adjacent to the MAD binding site within the quadrant enhancer. Our results demonstrate that Drifter functions along with MAD as a direct activator of Vestigial expression in the wing pouch.

Animals↗
PubMed1997

ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila.

Cell migration is an important step in a variety of developmental processes in many multicellular organisms. A particularly appropriate model to address the study of cell migration is the tracheal system of Drosophila, whose formation occurs by migration and fusion from clusters of ectodermal cells specified in each side of ten embryonic segments. Morphogenesis of the tracheal tree requires the activity of many genes, among them breathless (btl) and ventral veinless (vvl) whose mutations abolish tracheal cell migration. Activation of the btl receptor by branchless (bnl), its putative ligand, exerts an instructive role in the process of guiding tracheal cell migration. vvl has been shown to be required for the maintenance of btl expression during tracheal tree formation. Here we show that, in addition, vvl is independently required for the specific expression in the tracheal cells of thick veins (tkv) and rhomboid (rho), two genes whose mutations disrupt only particular branches of the tracheal system. Indeed, we show that expression in the tracheal cells of an activated form of tkv, the putative decapentaplegic (dpp) receptor, is able to induce shifts in their migration, asserting the role of the dpp pathway in establishing the branching pattern of the tracheal tree. In addition, by ubiquitous expression of the btl and tkv genes in vvl mutant embryos we show that both genes contribute to vvl function. These results indicate that through activation of its target genes, vvl makes the tracheal cells competent to further signalling and suggest that the btl transduction pathway could collaborate with other transduction pathways also regulated by vvl to specify the tracheal branching pattern.

Animals↗
PubMed1996

Transcriptional control of cell phenotypes in the neuroendocrine system.

A fundamental aspect of the development of complex organ systems is a requirement for precise temporal and spatial coordination in the genesis of tissues of distinct embryonic origins, in order to form functional units required for physiological homeostasis and survival. Such a requirement is particularly well exemplified in mammalian development in the formation of the hypothalamic-pituitary axis. Neuronally expressed POU domain factors might exert effects on terminal differentiation events similar to those of Pit-1 in the maturation of anterior pituitary gland cell phenotypes. Neurons comprising the endocrine hypothalamus develop in tandem with their ultimate target, the pituitary gland, and arise from a primordium in which three related class III POU domain factors-Brn-2, Brn-4, and Brn-1-are initially co-expressed. These factors subsequently exhibit stratified patterns of ontogenic expression, correlating with the appearance of distinct neuropeptides that define three major endocrine hypothalamic cell types. Deletion of the Brn-2 genomic locus affects terminal differentiation and/or maintenance of hypothalamic neurosecretory neurons and development of the posterior pituitary gland. Thus, both neuronal and endocrine components of the hypothalamic-pituitary axis are critically dependent upon the action of specific POU domain factors at a penultimate step in the sequential events that underlie the appearance of mature cellular phenotypes.

Amino Acid Sequence↗
PubMed1996

Specific up-regulation of the POU domain transcription factor Oct-2 following axotomy.

Peripheral nerve damage causes a dramatic alteration to the gene expression in primary sensory neurons, changes within the neuronal cell body giving rise to an altered phenotype, adapted for axonal regeneration. Such changes suggest an alteration in activity, or levels, of cellular transcription factors. The POU family transcription factor Oct-2 is known to be induced in sensory neurons by nerve growth factor (NGF) and might therefore be affected by the removal of target-derived NGF following axotomy. Paradoxically, however, the expression of Oct-2 showed a transient increase of two- to three-fold 24 h after axotomy. In contrast, axotomy had no effect on the levels of the Brn-3 sub-family of POU proteins, indicating that this effect was specific for Oct-2.

Animals↗
PubMed1996

Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons.

Immediate-early genes (IEGs) are widely used to mark endocrine hypothalamic neurons that are activated in response to stress, yet their relationship to the transcriptional control of relevant effector molecule expression is unclear. Acute ether stress provokes increased adrenocorticotropic hormone (ACTH) and corticosterone secretion that peaks at 5 and 30 min, respectively, after the challenge. Using probes complementary to intronic sequences of genes encoding ACTH secretagogues in parvocellular neurosecretory neurons of the paraventricular nucleus, we found these events to be accompanied by rapid and transient increases in corticotropin-releasing factor heteronuclear RNA (CRF hnRNA; peak at 5 min) and by a delayed upregulation of arginine vasopressin (AVP) hnRNA (120 min). To identify candidate mechanisms regulating peptide expression, we followed the timing of ether effects on representatives of three transcription factor classes: IEGs [c-fos and nerve growth factor I-B (NGFI-B)], a POU-domain factor (Brn-2), and the cAMP response element-binding protein (CREB), using antisera specific to its transcriptionally active, phosphorylated form (pCREB). After ether exposure, c-fos and NGFI-B mRNA induction were maximal at 30--60 min, whereas Fos protein peaked at 60--120 min. Brn-2 mRNA was expressed constitutively in the PVH and was unresponsive to stress. By contrast, pCREB was induced in parvocellular neurons with a time course parallel to that of CRF hnRNA expression. Stress-induced transcriptional activation of the CRF and AVP genes in hypophysiotropic neurons follows distinct time courses that are compatible with control mechanisms involving phosphorylation events and de novo protein synthesis, respectively.

Adrenocorticotropic Hormone↗
PubMed2001

The POU domain transcription factor Brn-3a protects cortical neurons from apoptosis.

We have demonstrated previously that exogenously expressed Brn-3a is capable of protecting neurons of the peripheral nervous system against apoptosis. In these previous studies Brn-3a showed a degree of neuronal sub-type specificity, in that while it could promote survival in NGF-dependent sensory neurons, no effect was observed in NGF-dependent neurons of the sympathetic nervous system. In this report, we show that Brn-3a delivered using a herpes simplex virus is capable of protecting cultures of rat cerebrocortical neurons of the central nervous system against two types of cell death stimuli, including glutamate neurotoxicity. Hence the protective effect of Brn-3a is not confined to neurons of the peripheral nervous system but can also occur in neurons of the CNS.

Animals↗
PubMed1992

Induction of the POU domain transcription factor Oct-2 during T-cell activation by cognate antigen.

Oct-2 is a transcription factor that binds specifically to octamer DNA motifs in the promoters of immunoglobulin and interleukin-2 genes. All tumor cell lines from the B-cell lineage and a few from the T-cell lineage express Oct-2. To address the role of Oct-2 in the T-cell lineage, we studied the expression of Oct-2 mRNA and protein in nontransformed human and mouse T cells. Oct-2 was found in CD4+ and CD8+ T cells prepared from human peripheral blood and in mouse lymph node T cells. In a T-cell clone specific for pigeon cytochrome c in the context of I-Ek, Oct-2 was induced by antigen stimulation, with the increase in Oct-2 protein seen first at 3 h after activation and continuing for at least 24 h. Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A, as well as by protein synthesis inhibitors. These results suggest that Oct-2 participates in transcriptional regulation during T-cell activation. The relatively delayed kinetics of Oct-2 induction suggests that Oct-2 mediates the changes in gene expression which occur many hours or days following antigen stimulation of T lymphocytes.

Animals↗
PubMed2002

Expression of Oct-6, a POU III domain transcription factor, in schizophrenia.

OBJECTIVE: Oct-6, a POU-III domain transcription factor, is expressed in embryonic stem cells and Schwann cells and in neuronal subpopulations during early mammalian development, but its relevance to disorders of cerebral development in humans is untested. This study evaluated the expression of Oct-6 in schizophrenia, a disorder that has been linked with neurodevelopmental abnormalities. METHOD: Immunohistochemistry was used to examine Oct-6 expression in the temporal lobe in postmortem tissue from 10 subjects with schizophrenia and 10 matched comparison subjects. Western blot analysis was used to study Oct-6 expression in the frontal and temporal cortex in tissue from an additional three schizophrenic and three matched comparison subjects and in the frontal lobe only in tissue from an additional 10 schizophrenic and 10 matched comparison subjects. RESULTS: Extensive Oct-6 immunoreactivity was present in the temporal lobe in all 10 schizophrenic subjects, while very little or no expression was found in the comparison subjects. In schizophrenic subjects, Oct-6 immunoreactivity was found in a subset of cells in the pyramidal cell layer of the hippocampus and in the granule cell layer of the dentate gyrus. Oct-6 staining was predominantly localized in the cytoplasm. Western blot analysis confirmed the presence of Oct-6 in the frontal and temporal cortex in schizophrenic subjects but not in comparison subjects. CONCLUSIONS: The presence of Oct-6 expression in the schizophrenic subjects but not in the comparison subjects suggests that Oct-6 may provide a marker for the neuropathology associated with schizophrenia. Further, it may provide a clue to the neurodevelopmental basis of the disease and could be a reliable means to examine the developmental brain abnormalities described in this disorder.

Adult↗
PubMed2005

Co-expression of SOX9 and SOX10 during melanocytic differentiation in vitro.

Investigations into pigment cell biology have relied on the ability to culture both murine and human melanocytes, numerous melanoma cell lines and more recently, murine and human melanoblasts. Melanoblast culture requires medium supplemented with a range of growth factors including Stem Cell Factor, Endothelin-3 and Fibroblast Growth Factor-2, withdrawal of which causes the cells to differentiate into melanocytes. Using the human melanoblast culture system, we have now examined the expression and/or DNA binding activity of several transcription factors implicated in melanocytic development and differentiation. Of these, the POU domain factor BRN2 and the SOX family member SOX10 are both highly expressed in unpigmented melanocyte precursors but are down-regulated upon differentiation. In contrast, the expression levels of the previously described MITF and PAX3 transcription factors remain relatively constant during the melanoblast-melanocyte transition. Moreover, BRN2 ablated melanoma cells lack expression of SOX10 and MITF but retain PAX3. A novel finding implicates a second SOX protein, SOX9, as a potential melanogenic transcriptional regulator, as its expression level is increased following the down-regulation of BRN2 and SOX10 in differentiated melanoblasts. Our results suggest that a complex network of transcription factor interactions requiring proper temporal coordination is necessary for acquisition and maintenance of the melanocytic phenotype.

Cell Differentiation↗
PubMed2005

A POU factor binding site upstream of the Chx10 homeobox gene is required for Chx10 expression in subsets of retinal progenitor cells and bipolar cells.

Retinal progenitor cells (RPCs) undergo a series of changes over time that affect their competency to produce different cell types at different times in development. The transcriptional machinery that regulates these changes, as well as associated gene expression changes, have not been characterized. An analysis of the regulatory region of the retinal homeodomain transcription factor, Chx10, was carried out using in ovo electroporations in chick and transgenic mice. An RPC enhancer was defined that mediates reporter activity in subsets of RPCs and directs high-level expression in intermediate and late RPCs. Using bioinformatic and biochemical analysis, a key binding site in this enhancer was found and was shown to be bound by the POU domain factors, Brn-2 and Tst-1/SCIP, in retinal extracts. Analysis of the Brn-2 expression pattern shows that it is expressed in intermediate and late RPCs, but not early RPCs, and thus partially overlaps with expression of the reporter activated by the defined Chx10 enhancer. Biochemical analysis also revealed binding of both Chx10 and Brn-2 to an enhancer of the CNS progenitor cell marker, Nestin. Nestin expression in the retina is restricted to intermediate/late RPC subsets, and genetic evidence is presented that demonstrates that Chx10 represses Nestin expression in early RPCs. A bipolar cell enhancer for Chx10 also was defined, and a role for Brn-2 in expression of Chx10 in bipolar cells is predicted. These data identify Brn-2 as a new marker of subsets of RPCs and suggest a mechanism by which a combination of POU factors and Chx10 define RPC gene expression patterns, such as that of Nestin.

Animals↗
PubMed2005

Brn1/2/4, the predicted midgut regulator of the endo16 gene of the sea urchin embryo.

A specific prediction of our detailed cis-regulatory analysis of the Strongylocentrotus purpuratus (Sp) endo16 gene was that the later expression of this gene would be driven by a midgut-specific transcriptional regulator. We have now identified this factor and determined some of its functions. The cDNA sequence reveals it to be a POU domain factor related closely to the mammalian factors Brain-1, -2, and -4. The factor was termed SpBrn1/2/4 (henceforth Brn1/2/4). Quantitative measurements of transcript prevalence show that the gene is first activated in the 20-h blastula, but there remain only about 100 molecules of brn1/2/4 mRNA per embryo (only a few per endoderm cell) until an abrupt 10-fold increase occurs as gastrulation begins. Measured in the same embryos, the late rise in prevalence of endo16 transcripts follows that of brn1/2/4 transcripts. As predicted by the endo16 model, brn1/2/4 expression is confined perfectly to the midgut, coincident with the domain of endo16 expression. The kinetics of accumulation of these transcripts indicates that the switch into the late phase of endo16 expression occurs when the brn1/2/4 transcript level nears its plateau (2000 molecules mRNA per embryo), after which each endo16 gene produces about 1 mRNA every 2 min (about 380 molecules mRNA per min in the whole embryo). Arrest of Brn1/2/4 translation by MASO treatment blocks the late phase of endo16 expression and specifically abolishes expression of cis-regulatory Module B of endo16, while not affecting Module A, also as predicted. The brn1/2/4 gene lies downstream of the regulatory genes executing post-gastrular specification of the midgut, as shown by further gene expression perturbation experiments which provide an initial glimpse of the underlying network architecture.

Amino Acid Sequence↗
PubMed2000

Regulation of central neuron synaptic targeting by the Drosophila POU protein, Acj6.

Mutations in the Drosophila class IV POU domain gene, abnormal chemosensory jump 6 (acj6), have previously been shown to cause physiological deficits in odor sensitivity. However, loss of Acj6 function also has a severe detrimental effect upon coordinated larval and adult movement that cannot be explained by the simple loss in odorant detection. In addition to olfactory sensory neurons, Acj6 is expressed in a distinct subset of postmitotic interneurons in the central nervous system from late embryonic to adult stages. In the larval and adult brain, Acj6 is highly expressed in central brain, optic and antennal lobe neurons. Loss of Acj6 function in larval optic lobe neurons results in disorganized retinal axon targeting and synapse selection. Furthermore, the lamina neurons themselves exhibit disorganized synaptic arbors in the medulla of acj6 mutant pupal brains, suggesting that Acj6 may play a role in regulating synaptic connections or structure. To further test this hypothesis, we misexpressed two Acj6 isoforms in motor neurons where they are not normally found. The two Acj6 isoforms are produced from alternatively spliced acj6 transcripts, resulting in significant structural differences in the amino-terminal POU IV box. Acj6 misexpression caused marked alterations at the neuromuscular junction, with contrasting effects upon nerve terminal branching and synapse formation associated with specific Acj6 isoforms. Our results suggest that the class IV POU domain factor, Acj6, may play an important role in regulating synaptic target selection by central neurons and that the amino-terminal POU IV box is important for regulation of Acj6 activity.

Alternative Splicing↗
PubMed2003

Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way.

Aging↗