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 469 records · Page 26Linked to original sources
PubMed2006

Targeting Brn-3b in breast cancer therapy.

The Brn-3b POU domain transcription factor is elevated in a significant proportion of breast cancers and in neuroblastoma tumours, where it is associated with increased proliferation, anchorage-independent growth, faster and larger tumour growth in xenograft models, resistance to growth inhibitory stimuli and increased migratory potential. These effects are associated with the ability of Brn-3b to regulate specific genes associated with these processes. Reducing Brn-3b can reverse many of these effects, suggesting that it may be possible to alter the growth and behaviour of tumour cells by abrogating Brn-3b in these cancers. This review discusses the effect of altering Brn-3b in these cancer cells and possible approaches to targeting Brn-3b as a strategy for therapy in treatment of breast cancers.

Amino Acid Sequence↗
PubMed2006

Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells.

The POU domain transcription factor OCT4 is a key regulator of pluripotency in the early mammalian embryo and is highly expressed in the inner cell mass of the blastocyst. Consistent with its essential role in maintaining pluripotency, Oct4 expression is rapidly downregulated during formation of the trophoblast lineage. To enhance our understanding of the molecular basis of this differentiation event in humans, we used a functional genomics approach involving RNA interference-mediated suppression of OCT4 function in a human ESC line and analysis of the resulting transcriptional profiles to identify OCT4-dependent genes in human cells. We detected altered expression of >1,000 genes, including targets regulated directly by OCT4 either positively (NANOG, SOX2, REX1, LEFTB, LEFTA/EBAF DPPA4, THY1, and TDGF1) or negatively (CDX2, EOMES, BMP4, TBX18, Brachyury [T], DKK1, HLX1, GATA6, ID2, and DLX5), as well as targets for the OCT4-associated stem cell regulators SOX2 and NANOG. Our data set includes regulators of ACTIVIN, BMP, fibroblast growth factor, and WNT signaling. These pathways are implicated in regulating human ESC differentiation and therefore further validate the results of our analysis. In addition, we identified a number of differentially expressed genes that are involved in epigenetics, chromatin remodeling, apoptosis, and metabolism that may point to underlying molecular mechanisms that regulate pluripotency and trophoblast differentiation in humans. Significant concordance between this data set and previous comparisons between inner cell mass and trophectoderm in human embryos indicates that the study of human ESC differentiation in vitro represents a useful model of early embryonic differentiation in humans.

Apoptosis↗
PubMed1999

Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear.

Targeted mutagenesis in mice demonstrates that the POU-domain gene Brn4/Pou3f4 plays a crucial role in the patterning of the mesenchymal compartment of the inner ear. Brn4 is expressed extensively throughout the condensing mesenchyme of the developing inner ear. Mutant animals displayed behavioral anomalies that resulted from functional deficits in both the auditory and vestibular systems, including vertical head bobbing, changes in gait, and hearing loss. Anatomical analyses of the temporal bone, which is derived in part from the otic mesenchyme, demonstrated several dysplastic features in the mutant animals, including enlargement of the internal auditory meatus. Many phenotypic features of the mutant animals resulted from the reduction or thinning of the bony compartment of the inner ear. Histological analyses demonstrated a hypoplasia of those regions of the cochlea derived from otic mesenchyme, including the spiral limbus, the scala tympani, and strial fibrocytes. Interestingly, we observed a reduction in the coiling of the cochlea, which suggests that Brn-4 plays a role in the epithelial-mesenchymal communication necessary for the cochlear anlage to develop correctly. Finally, the stapes demonstrated several malformations, including changes in the size and morphology of its footplate. Because the stapes anlage does not express the Brn4 gene, stapes malformations suggest that the Brn4 gene also plays a role in mesenchymal-mesenchymal signaling. On the basis of these data, we suggest that Brn-4 enhances the survival of mesodermal cells during the mesenchymal remodeling that forms the mature bony labyrinth and regulates inductive signaling mechanisms in the otic mesenchyme.

Acoustic Stimulation↗
PubMed1999

Retinoblastoma protein expression leads to reduced Oct-1 DNA binding activity and enhances interleukin-8 expression.

Tumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-gamma treatment, and reconstitution of functional Rb rescues IFN-gamma-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unknown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain transcription factor, was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1, thus relieving its repressive effect. Oct-1 has also been shown to repress interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expression is higher in these cell lines.

Blotting, Western↗
PubMed2001

Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice.

Brn3a/Brn-3.0 is a POU-domain transcription factor expressed in primary sensory neurons of the cranial and dorsal root ganglia and in specific neurons in the caudal CNS. Mice lacking Brn3a undergo extensive sensory neural death late in gestation and die at birth. To further examine Brn3a expression and the abnormalities that accompany its absence, we constructed a transgene containing 11 kb of Brn3a upstream regulatory sequence linked to a LacZ reporter. Here we show that these regulatory sequences direct transgene expression specifically to Brn3a peripheral sensory neurons of the cranial and dorsal root ganglia. Furthermore, expression of the 11 kb/LacZ reporter in the sensory neurons of the mesencephalic trigeminal, but not other Brn3a midbrain neurons, demonstrates that cell-specific transgene expression is targeted to a functional class of neurons rather than to an anatomical region. We then interbred the 11 kb/LacZ reporter strain with mice carrying a null mutant allele of Brn3a to generate 11 kb/LacZ, Brn3a knock-out mice. beta-Galactosidase expression in these mice reveals significant axonal growth defects, including excessive and premature branching of the major divisions of the trigeminal nerve and a failure to correctly innervate whisker follicles, all of which precede sensory neural death in these mice. These defects in Brn3a(-/-) mice resemble strongly those seen in mice lacking the mediators of sensory pathfinding semaphorin 3A and neuropilin-1. Here we show, however, that sensory neurons are able to express neuropilin-1 in the absence of Brn3a.

Animals↗
PubMedDate not supplied

Molecular characterization of a novel BR-2 gene that is down-regulated in human low grade glioma tumors.

Using the technique of differential hybridization of a human fetal brain library, we have identified a novel gene, brain 2 (BR-2). This gene is expressed in normal brain but has low or no expression in human oligodendrogliomas and other brain tumor samples. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-2. BR-2 sequence showed strong homolog to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-2 and an EST from a human placenta library. Multiple tissue dot blot analysis indicated that the BR-2 gene is expressed in a number of tissues including brain, heart, lung, placenta, lymph node, trachea and kidney. The BR-2 gene is also expressed in fetal heart, spleen and lung tissue. An extremely high level of BR-2 expression is observed in the left atrium of the heart. Low or no expression of BR-2 expression is observed in sixteen human cancer cell lines. RT-PCR analysis indicated that the BR-2 gene is expressed at high levels in two of the five normal brain tissue samples analyzed. Except for low expression in one oligodendroglioma, no expression of BR-1 gene was observed in eight anaplastic astrocytomas and glioblastoma multiforme tissue samples. Four of nine glioblastoma tumor cell lines did show a low level of BR-2 expression. On the basis of its expression and sequence, we conclude that BR-2 is a novel gene with unique expression properties in human brain tumors.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning, sequencing and expression analysis of a novel gene BR-1 that is expressed in normal human brain tissue but not in glioma tumor samples.

Using the technique of differential hybridization of a human fetal brain library, we identified a novel gene, brain 1 (BR-1). This gene is expressed in normal brain but has low or no expression in human gliomas. We have cloned and sequenced the full-length cDNA corresponding to this gene. A data base search for the nucleotide sequence homology was performed for BR-1. The BR-1 sequence showed strong homology to a human genomic clone from chromosome 2. Moderate sequence homology was observed between BR-1 and an expressed sequence tag (EST) from a human placenta library. Three different regions of BR-1 also showed homology to a mouse EST that is similar to EL-10 gene. Sequence analysis indicated that the protein sequence for BR-1 has one tyrosine kinase phosphorylation site and two N-myristoylation sites. Northern blot analysis indicated that the BR-1 gene is expressed in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas. A low level of expression of BR-1 is observed in the cerebellum, cerebral cortex, spinal cord, occipital lobe and putamen. The BR-1 gene is also expressed in fetal brain, liver and kidney. Low expression of BR-1 gene was observed in a number of non-brain tumor cell lines. RT-PCR analysis indicated that the BR-1 gene was expressed in non-neoplastic (epilepsy specimens) but not in six oligodendrogliomas and three oligoastrocytoma tumor samples analyzed. BR-1 was not expressed in either seven low grade gliomas or eight grade IV glioblastoma tumor tissue samples analyzed. Three glioblastoma cell lines did show low expression of the BR-1 gene. On the basis of its expression properties, we conclude that BR-1 is a potential novel tumor suppressor gene.

Base Sequence↗
PubMed2001

[Establishment of two-dimensional gel electrophoretic protein map of human spermatozoa].

OBJECTIVE: To establish the method of 2-dimensional electrophoresis(2-DE) for proteins of human spermatozoa and to construct a protein map of human spermatozoa. METHODS: The sperm pellet was prepared with simple Percoll layer protocol. We studied the effects of various sample preparation methods, loading quantities and isoelectric-focusing protocols on the quality of silver-stained 2-DE map, and constructed a primary protein map of human spermatozoa. RESULT: Up to 703 protein spots were acquired with sample preparation Method I while only 194-210 spots with Method II. With immobilized pH gradients and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(IPG-DALT) we could acquire over 700 spots while only 280-300 with isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(ISO-DALT). CONCLUSION: It is satisfactory to lyse sperm with sample preparation Method I and to separate sperm proteins by IPG-DALT for establishing 2-D map of human sperm.

Adult↗
PubMed2004

[The progress in complex homeobox domains].

The proteins with 'homeobox' (HOX) domain, a large family of DNA binding, play an important role in embryonic development, gene regulation, cell differentiation and neurogenesis. Some other domains are found in the proteins together with HOX, such as PAX, POU, LIM, OAR, ELK, SIX, bZIP, PHD-finger, Engrailed, hexapeptide domains. The HOX combined with other domains that associate with DNA binding or protein interactions are called 'complex homeobox'. Recent reports indicate that 'complex homeobox' genes also take part in tumorigenesis by the way of gene fusions and deregulation. The progress of 'complex homeobox' in types, structures and functions have been summarized in this review.

Animals↗
PubMed2005

Comparative genomics on SFRP2 orthologs.

SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, DKK1, DKK2, DKK3, DKK4, and WIF1 are soluble modulators of WNT signaling. SFRP2 gene at human chromosome 4q31.3 is claimed as a tumor suppressor gene inactivated by the epigenetic CpG hypermethylation in colorectal cancer. SFRP2 methylation is a sensitive single DNA-based marker for the fecal screening of colorectal cancer. On the other hand, SFRP2 is claimed to induce cellular resistance to apoptosis in mammary tumors. Here, we identified and characterized the rat Sfrp2 gene by using bioinformatics. Rat Sfrp2 gene, consisting of three exons, was located within AC129161.3 genome sequence. Rat Sfrp2 gene was found to encode a 295-aa Sfrp2 protein, consisting of signal peptide, Frizzled domain with ten conserved Cys residues, and Netrin (NTR) domain with six conserved Cys residues. Rat Sfrp2 showed 98.6% and 97.6% total-amino-acid identity with mouse Sfrp2 and human SFRP2, respectively. Phylogenetic analyses revealed that Sfrp2 orthologs were more related to Sfrp1 and Sfrp5 orthologs than to Sfrp3 and Sfrp4 orthologs. Human SFRP2 promoter (nucleotide position 71417-71152 of AC020703.7 genome sequence) and rat Sfrp2 promoter (nucleotide position 184090-184357 of AC129161.3 genome sequence) showed 88.7% total nucleotide identity. GC content of human SFRP2 promoter was 63.9%. Binding site for POU domain transcription factors (POU2F1, POU2F2, etc.) was conserved between human SFRP2 promoter and rat Sfrp2 promoter. SFRP2 mRNA was expressed in embryonic stem (ES) cells, diffuse type gastric cancer with signet ring cell features, pancreatic cancer, colorectal cancer, retinoblastoma, and insulinoma. This is the first report on comparative integromics analyses on SFRP2 orthologs.

Amino Acid Sequence↗
PubMed2005

[Detection of POU3F4 gene mutations in the Chinese pedigree with Y-linked hereditary hearing impairment].

OBJECTIVE: To analyze the mutations of candidate POU3F4 gene in the Chinese pedigree with Y linked hereditary hearing impairment. METHODS: Polymerase chain reaction (PCR) reactions were performed with five pairs of primer in the coding sequence of POU3F4 gene. PCR-single-strand conformation polymorphism (PCR-SSCP) was subsequently applied in the 43 individuals of DFNY1 family for screening the gene mutations. RESULTS: The PCR amplification fragments showed well quality in the five pairs of primer and further analysis with PCR-SSCP showed no any polymorphism and mutations in the members. CONCLUSIONS: The possibility of the deafness gene POU3F4, which locates on the translocation region on X and Y chromosome, contributed to the Y linked family deafness was successfully ruled out. It may imply that the causal gene of the DFNY1 family locate on the Y chromosome.

Adolescent↗
PubMed2005

Localization of rDNA sites in holocentric chromosomes of three species of triatomines (Heteroptera, Triatominae).

Chromatin organization in the holocentric chromosomes of three triatomines species was cytologically studied by fluorescent in situ hybridization with a 45S rDNA probe of Drosophila melanogaster to localize ribosomal genes. In Triatoma tibiamaculata, metaphases I showed telomeric highlights in a single, larger bivalent. In T. protacta, hybridization was detected in one of the telomeres of an autosomal chromosome. In T. platensis, there were highlights in a single, smaller chromosome (X chromosome). The results obtained did not agree with the expected localization of rDNA genes in the sex chromosomes of triatomines, as demonstrated by silver impregnation, and suggest that the chromosome reorganization that occurred in this group during evolution may be a more important mechanism involved in rDNA distribution.

Animals↗
PubMed2006

Clinics in diagnostic imaging (111): X-linked congenital mixed deafness syndrome.

Two siblings, boys aged five and six years old, presented with mixed hearing loss. Computed tomography of the temporal bones showed bulbous dilatation of the internal auditory canals and incomplete separation with the basal turn of the cochlear, consistent with the diagnosis of X-linked congenital progressive mixed deafness syndrome. The diagnosis and management of this rare condition is discussed.

Child↗