Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “POU Domain Factors”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed1995

Mutation of the Oct-1 POU-specific recognition helix leads to altered DNA binding and influences enhancement of adenovirus DNA replication.

To assess which residues of Oct-1 POU-specific (POUs) are important for DNA recognition and stimulation of adenovirus DNA replication we have mutated 10 residues of the POUs helix-turn-helix motif implicated in DNA contact. Seven of these turned out to have reduced DNA binding affinity. Of these, three alanine substituted proteins were found to have a changed specificity using a binding site selection procedure. Mutation of the first residue in the recognition helix, Gln44, to alanine led to a loss of specificity for the first two bases, TA, of the wild-type recognition site TATGC(A/T)AAT. Instead of the A, a T was selected, suggesting a new contact and a novel specificity. A change in specificity was also observed for the T45A mutant, which could bind to TATAC(A/T)AAT, a site hardly recognized by the wild-type protein. Mutation of residue Arg49 led to a relaxed specificity for three consecutive bases, TGC. This residue, which is critical for high affinity binding, is absent from the structurally homologous lambdoid helix-turn-helix motifs. Employing a reconstituted system all but two mutants could stimulate adenovirus DNA replication upon saturation. Mutation of residues Gln27 and Arg49 impairs the ability of the Oct-1 POU domain protein to enhance replication, with a concomitant loss of DNA contacts. Since the POU domain binds the precursor terminal protein-DNA polymerase complex and guides it to the origin, lack of stimulation may be caused by incorrect targetting of the DNA polymerase due to loss of specificity.

Adenoviridae↗
PubMed2002

Oct-2 regulates CD36 gene expression via a consensus octamer, which excludes the co-activator OBF-1.

The POU domain transcription factor, Oct-2, is essential for the B cell-specific expression of CD36 in mouse B cells. In order to determine how Oct-2 mediates expression of CD36 in B cells, we cloned and analysed the mouse CD36 promoter. In contrast to the human CD36 promoter, the mouse promoter contains a consensus octamer element of the type ATGCTAAT. This octamer element can be bound by either Oct-1 or Oct-2 but requires the expression of Oct-2 to activate transcription in B cells. Mutation of the octamer element renders the CD36 promoter refractory to activation by Oct-2. Furthermore, we demonstrate that the CD36 octamer element does not support recruitment of the B cell-specific co-activator OBF-1 and that CD36 expression is unaffected in primary B cells derived from obf-1(-/-) mice. We conclude that Oct-2 activates CD36 gene expression in mouse B cells via the octamer element in the promoter. Our data also demonstrate that CD36 is the first example of an Oct-2-dependent gene whose expression in B cells is independent of OBF-1. These findings support the notion that Oct-2 regulates gene transcription by both OBF-1-dependent and -independent mechanisms.

Animals↗
PubMed2006

AliWABA: alignment on the web through an A-Bruijn approach.

UNLABELLED: Multiple sequence alignment programs are an invaluable tool in computational biology. A-Bruijn Alignment (ABA) is a method for multiple sequence alignment that represents an alignment as a directed graph and has proved useful in aligning nucleotide and amino acid sequences that are composed of repeated and shuffled subsequences. AliWABA is a web server that provides tools to generate alignments with ABA, visualize the resulting ABA graphs and extract subsequences from ABA graphs. AliWABA greatly simplifies the problem of analyzing multiple sequences for local similarities that may be reordered, as is common with the domain architectures of proteins. To facilitate the analysis of protein domains, AliWABA provides direct querying of the Conserved Domain Database. AVAILABILITY: http://aba.nbcr.net/

Algorithms↗
PubMed2004

Pluripotent lineage definition in bovine embryos by Oct4 transcript localization.

The POU-domain transcription factor Pou5f1 (Oct4) is restricted to pluripotent embryonic cells and the germ line of the mouse and is required for the maintenance of pluripotency of cells within the inner cell mass of the mouse blastocyst. Despite highly conserved genomic organization and regulatory regions between the mouse Oct4 gene and its bovine orthologue, bovine Oct4 protein is not restricted to the inner cell mass of blastocyst-stage embryos, suggesting that Oct4 may not be a key regulator of pluripotency in the bovine. We analyze the temporal and spatial distribution of Oct4 transcript in bovine oocytes and preimplantation-stage embryos, and in contrast to protein distribution, we find strong conservation between bovine and mouse. Oct4 transcript is present at low levels in the bovine oocyte. Similar to mouse, bovine Oct4 transcription begins one to two cell cycles after zygotic genome activation, followed by a sharp increase in transcription subsequent to compaction. Oct4 transcript is ubiquitously present in all cells of embryos at the morula stage; however, in Day 7 bovine blastocysts, Oct4 signal is not visible in the trophectoderm by in situ hybridization, indicating that transcriptional downregulation of Oct4 on differentiation is similar to that observed in mouse and other mammals. These results indicate that in contrast to protein distribution, regulation of Oct4 transcription is conserved between mammalian species.

Animals↗
PubMed2003

Unaltered expression of Bcl-2 and TAG-1/axonin-1 precedes sensory apoptosis in Brn3a knockout mice.

Mice lacking the POU-domain transcription factor Brn3a exhibit growth defects in trigeminal axons, undergo extensive sensory cell death in late gestation, and die at birth. Based on tissue culture studies, the mediator of apoptosis Bcl-2 has been suggested as a target of Brn3a regulation which could affect sensory viability in these mice. In addition, Bcl-2 and the neural cell adhesion molecule TAG-1/axonin-1 have both been implicated in sensory axon guidance. In this study we examined wild-type and Brn3a knockout embryos for alterations in the expression of these genes. Trigeminal ganglia were harvested from embryonic day 13.5 mouse embryos, and Bcl-2 and TAG-1 expression were measured by RT-PCR. TAG-1 expression was also examined in the embryonic trigeminal and dorsal root ganglia by immunohistochemistry. The developing trigeminal ganglia of Brn3a knockout mice exhibit similar levels of Bcl-2 and TAG-1 mRNA expression. Immunohistochemical staining of TAG-1 also appeared to be quantitatively similar in the sensory axons of wild-type and knockout embryos. It is unlikely that Bcl-2 is a regulatory target of Brn3a, or that either of these factors mediates the defects in axon guidance and neuronal survival observed in the sensory ganglia of Brn3a knockout mice.

Animals↗
PubMed1998

A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3).

OBJECTIVE: The molecular defect in patients with X-linked mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene. STUDY DESIGN: This was a genetic study of a single Japanese family with DFN3. METHODS: Products of a polymerase chain reaction (PCR) were subjected to single-strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR products from patients and carriers showing SSCP variants was performed using the fluorescent dideoxy termination method and a sequencer. RESULTS: Sequencing of the PCR product revealed a 6-base deletion (TTCAAA) at nucleotides 601 to 606, resulting in a two-amino-acid deletion in the POU3F4 protein, (phenylalanine and lysine at amino acid residues 201 and 202). The deletion was adjacent to the site of a nonsense mutation previously described. CONCLUSION: Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations.

Asian People↗
PubMed1998

Redox regulation of Brn-2/N-Oct-3 POU domain DNA binding activity and proteolytic formation of N-Oct-5 during melanoma cell nuclear extraction.

Reversible oxidation sensitivity of N-Oct-3 DNA binding activity was seen when melanoma extracts and recombinant Brn-2 protein were treated with a variety of metals, hydrogen peroxide and the cysteine disulphide bond forming agent diamide. Western blot analysis of diamide-oxidized N-Oct-3 protein indicated that this was likely to be due to intramolecular disulphide bonding. The potential role of oxidative loss of N-Oct-3 DNA binding activity is discussed in relation to redox changes that may occur during the early phase of apoptosis in neuronal cell lines and tissues. Brn-2 C-terminal antibody Western blot analysis of melanoma cell line nuclear extracts prepared using a combination of sodium dodecyl sulphate and NP-40 detergent cell lysis procedures demonstrated the formation of N-Oct-5 DNA binding activity via N-terminal proteolytic clipping of Brn-2/N-Oct-3.

Animals↗
PubMed2006

A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family.

OBJECTIVES/HYPOTHESIS: It is known that approximately 5% of congenital profound hearing impaired cases are inherited in X-linked inheritance. This study aimed at identifying its underlying molecular determinant(s) using a large, five-generation Chinese family with multiple familial cases. STUDY DESIGN: Model-based linkage analysis and positional cloning. METHODS: Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine disease locus. Mutation screening was performed within the family and unrelated population-based controls to establish molecular evidence as to what caused the specific X-linked inheritance pattern in the family. RESULTS: Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.I-Xq23 (maximum X-linkage logarithm of odds score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T>C) in the well-known deaf gene. POU3F4. Direct sequencing on 240 unrelated controls did not detect any mutation. CONCLUSIONS: Multiple analysis approaches demonstrated that these disorders in the family were caused by a founder mutation in the POU3F4 gene. Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene.

Adolescent↗
PubMed2005

Wilms tumor in monozygous twins: clinical, pathological, cytogenetic and molecular case report.

The concomitant occurrence of Wilms tumor (WT) was observed in two monozygotic twin sisters without evidence of congenital malformations. Twin 1 was diagnosed with a stage I WT at 11 months of age, whereas twin 2 developed a bilateral (stage V) WT at 13 months of age. In both cases pathologic examination showed a nonanaplastic stromal type WT, with marked rhabdomyomatous elements. Cytogenetic analyses performed on blood samples and on tumor specimens revealed no karyotypic abnormality. No alteration of the WT1 and POU6F2 genes was identified in constitutional and tumor DNA of both sisters, and no anomaly in WT1 expression was evidenced in the normal kidney of one of them. However, loss of heterozygosity on chromosome 11p, involving the alleles of maternal origin, was detected both in the single tumor of twin 1 and in the two distinct tumors of twin 2, thus suggesting a common etiology of the diseases. To the authors' knowledge, this is the first report describing at both the clinical and genetic level a couple of monozygotic twins concordant for WT development.

Child, Preschool↗
PubMed2005

OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma.

OCT4 is an 18-kDa POU-domain transcription factor encoded by the POU5F1 gene. Also known as OCT3, OTF3, and POU5F1, OCT4 is involved in the initiation, maintenance, and differentiation of pluripotent and germline cells during normal development. It is expressed in mouse and human embryonic stem and germ cells but absent from all differentiated somatic cell types in vitro and in vivo. OCT4 has been detected in primary testicular germ cell tumors with pluripotent potential: seminoma and embryonal carcinoma. We investigated: 1) whether a similar pattern of expression is present in primary intracranial germinomas; and 2) how OCT4 compares with placental alkaline phosphatase (PLAP) in terms of specificity and sensitivity as a potential diagnostic tool. We examined histologic sections from 25 cases of germinoma in which paraffin blocks with sufficient material were available. All cases were reviewed and sections from 32 different blocks were obtained and immunostained for OCT4 and PLAP. Additionally, 49 primary and metastatic brain tumors that may be potentially confused with germinoma, either clinically or histologically, were investigated for OCT4 expression. All but one germinoma were pure (ie, lacking other germ cell components). Intense and often diffuse nuclear staining was detected in 100% of germinomas. PLAP immunoreactivity was detected in 23 of 25 cases and was absent in the remaining 2 cases. The intensity of OCT4 immunostaining was significantly better than that of PLAP. None of the 49 control cases, which included glioblastoma multiforme, pineoblastoma, pituitary adenoma, malignant lymphoma, metastatic melanoma, capillary hemangioblastoma, meningioma, schwannoma, and a variety of metastatic carcinomas showed immunoreactivity for OCT4. Our study demonstrates that OCT4 is a highly specific and sensitive immunohistochemical marker for primary intracranial germinomas. OCT4 should be part of immunoperoxidase staining panels in which germinoma enters the differential diagnosis.

Alkaline Phosphatase↗
PubMed1996

Lineage-specific regulators couple cell lineage asymmetry to the transcription of the Caenorhabditis elegans POU gene unc-86 during neurogenesis.

The POU homeo box gene unc-86 specifies neuroblast and neural identities in the developing Caenorhabditis elegans nervous system. After an asymmetric neuroblast division, unc-86 is expressed in one of two daughter cells in 27 lineage classes that are not obviously related by function or position. We show here that unc-86 transcriptional regulatory regions detect cell lineage asymmetry to activate unc-86 expression in one of two neuroblast daughter cells. Distinct regulatory regions activate unc-86 expression in particular sets of sublineages. Therefore the unc-86 regulatory region integrates distinct cell lineage asymmetry cues to activate unc-86 expression in the many classes of neuroblast cell lineages. In agreement with such lineage-specific regulation of unc-86 asymmetric activation, mutations in lin-11 (LIM homeo box), ham-1, and lin-17 affect the asymmetry of unc-86 expression in particular cell lineages, and mutations in lin-32 (achaete/scute family), vab-3 (Pax-6 homolog) and egl-5 (Abd-B homolog) affect the establishment of unc-86 expression in other cell lineages. Homologs of unc-86 and many of these unc-86 regulators have been implicated in control of neurogenesis in vertebrates and invertebrates. These data suggest that unc-86 acts in a phylogenetically conserved pathway that couples neuroblast cell lineage asymmetry to the generation of diverse neural types.

Animals↗
PubMed1996

Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.

The terminal differentiation of myelinating glia involves complex interactions that culminate in the formation of myelin. The POU domain transcription factor Tst-1/Oct-6/SCIP is expressed transiently during myelination, and we report here that it has a critical role in this developmental process. Deletion of the Tst-1/Oct-6/SCIP gene produces a severe defect in peripheral myelination by arresting Schwann cell maturation before axonal wrapping. Unexpectedly, the activation of major myelin-specific genes appears to be unaffected by the Tst-1/Oct-6/SCIP mutation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-1/Oct-6/SCIP mutant homozygotes is associated with a fatal breathing defect, providing a model for investigating the regulation of pulmonary homeostasis.

Animals↗
PubMed2000

Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes.

The Wingless signaling pathway directs many developmental processes in Drosophila by regulating the expression of specific downstream target genes. We report here that the product of the trithorax group gene osa is required to repress such genes in the absence of the Wingless signal. The Wingless-regulated genes nubbin, Distal-less, and decapentaplegic and a minimal enhancer from the Ultrabithorax gene are misexpressed in osa mutants and repressed by ectopic Osa. Osa-mediated repression occurs downstream of the up-regulation of Armadillo but is sensitive both to the relative levels of activating Armadillo/Pangolin and repressing Groucho/Pangolin complexes present and to the responsiveness of the promoter to Wingless. Osa functions as a component of the Brahma chromatin-remodeling complex; other components of this complex are likewise required to repress Wingless target genes. These results suggest that altering the conformation of chromatin is an important mechanism by which Wingless signaling activates gene expression.

Animals↗
PubMed1995

On the functional overlap between two Drosophila POU homeo domain genes and the cell fate specification of a CNS neural precursor.

The approximately 200 distinct neurons comprising each hemisegment of the Drosophila embryonic CNS are derived from a stereotypic array of approximately 30 progenitor stem cells, called neuroblasts (NBs). Each NB undergoes repeated asymmetric divisions to produce several smaller ganglion mother cells (GMCs), each of which, in turn, divides to produce two neurons and/or glia cells. To understand the process by which cell type diversity is generated in the CNS, we are focusing on identifying genes that affect cell identity in the NB4-2 lineage from which the RP2 motoneuron is derived. We show here that within the early part of the NB4-2 lineage, two closely linked and structurally related POU homeo domain genes, pdm-2 (dPOU28) and pdm-1 (dPOU19), both encode proteins that accumulate to high levels only in the first GMC (GMC4-2a) and not in its progeny, the RP2 motoneuron. Our results from the genetic and developmental analysis of pdm-1 and pdm-2 demonstrate that these genes are not required for the birth of GMC4-2a; however, they are both involved in specifying the identity of GMC4-2a and, ultimately, in the genesis of RP2 neurons, with pdm-2 being the more dominant player in this process. In mutant animals where both pdm-1 and pdm-2 functions are removed, GMC4-2a fails to express markers consistent with a GMC4-2a identity and no mature (Eve protein expressing) RP2 neurons are produced. We demonstrate that in some mutant combinations in which no mature RP2 neurons are produced, some GMC4-2a cells can nevertheless divide. Hence, the failure of the POU mutants to produce mature RP2 neurons is not attributable to a block in GMC4-2a cell division per se but, rather, because the GMC4-2a cells fail to acquire their correct cellular identity.

Animals↗
PubMed2002

Control of neuronal subtype identity by the C. elegans ARID protein CFI-1.

The Caenorhabditis elegans hermaphrodite nervous system is composed of 302 neurons that fall into at least 118 diverse classes. Here we describe cfi-1, a gene that contributes to the development of neuronal diversity. cfi-1 promotes appropriate differentiation of the URA sensory neurons and inhibits URA from expressing the male-specific CEM neuronal fate. The UNC-86 POU homeodomain protein is present in CEM and URA neurons, and can promote expression of CEM-specific genes in both CEM and URA, but CFI-1 inhibits expression of these genes in the URA cells. cfi-1 also promotes appropriate differentiation and glutamate receptor expression in the AVD and PVC interneurons. cfi-1 encodes a conserved neuron- and muscle-restricted DNA-binding protein containing an A/T rich interaction domain (ARID). ARID proteins regulate early patterning and muscle fate in Drosophila, but they have not previously been implicated in the control of neuronal subtype identity.

Animals↗
PubMed2002

Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons.

Formation of highly organized neocortical structure depends on the production and correct placement of the appropriate number and types of neurons. POU homeodomain proteins Brn-1 and Brn-2 are coexpressed in the developing neocortex, both in the late precursor cells and in the migrating neurons. Here we show that double disruption of both Brn-1 and Brn-2 genes in mice leads to abnormal formation of the neocortex with dramatically reduced production of layer IV-II neurons and defective migration of neurons unable to express mDab1. These data indicate that Brn-1 and Brn-2 share roles in the production and positioning of neocortical neuron development.

Animals↗