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We have cloned a 36-kilobase segment of chicken DNA containing the gene coding for glyceraldehyde-3-phosphate dehydrogenase [GAPDH (EC 1.2.1.12)], a glycolytic enzyme which is expressed constitutively in all cell types. Using defined segments of this cloned DNA as probes, we have determined the DNase I sensitive domain of the GAPDH natural gene in the hen oviduct. When nuclei isolated from hen oviduct were treated with DNase I under conditions known to preferentially degrade actively transcribed genes (i.e., 15-20% of the DNA rendered perchloric acid soluble), a region of approximately 12 kilobase(s) (kb) containing the GAPDH coding sequences and flanking DNA was found to be highly susceptible to digestion by DNase I. Approximately 4 kb downstream from the end of the coding sequences, there was an abrupt transition from the DNase I sensitive or "open" configuration to the resistant or "closed" configuration. The chromatin then remained in a closed conformation for at least 10 kb further downstream. On the 5' side of the gene, the transition from a sensitive to a resistant configuration was located about 4 kb upstream from the gene. In addition, we have localized two repeated sequences in the area of DNA that was cloned. One of these is of the CR1 family of middle repetitive elements. It is located about 18 kb 3' to the gene and as such lies well outside of the DNase I sensitive region which encompasses GAPDH. The other repetitive element is of an uncharacterized family. It is located upstream from the gene and appears to be within a region of transition from the DNase I sensitive to resistant states.

RNA was transcribed from chick oviduct chromatin and the concentration of ovalbumin mRNA sequences in the RNA transcripts was measured by hybridization with a radioactive complementary DNA probe synthesized against purified ovalbumin mRNA using viral reverse transcriptase. Ovalbumin mRNA sequences were more abundant in RNAs transcribed from chromatin of estrogen-stimulated chick oviduct than that of chicks withdrawn from hormone. Reconstitution experiments indicated that the nonhistone protein fraction of the estrogen-stimulated chromatin was responsible for maintaining expression of the ovalbumin gene in vitro . In order to study the specific interactions between these regulatory proteins and the ovalbumin gene, we attempted to synthesize, isolate and amplify this gene. Using reverse transcriptase and the complete ovalbumin complementary DNA (cDNA ov ) as a template, a double-stranded DNA (the synthetic ovalbumin gene) was synthesized in vitro . This double-stranded synthetic ovalbumin gene has been successfully incorporated into bacterial plasmids and amplified. By an alternative method designed to obtain DNA sequences adjacent to the coding portion of the ovalbumin gene, we have also purified the natural ovalbumin gene from total chick DNA by affinity chromatography. Using separate columns in which purified ovalbumin mRNA (mRNA ov ) and CDNAOV were covalently linked to phospho-cellulose, the respective complementary ovalbumin DNA strands were enriched about 10, 000-fold from total chick DNA sheared mechanically to a mean length of four to five thousand base pairs. RNA transcribed from these partially purified DNA preparations contained ovalbumin sequences in a much greater concentration than RNA synthesized from total chick DNA.

A mathematical model for passive optical sensors, which takes into account the inherent shot-noise process, is presented. Based on this sensor model, the Cramer-Rao bounds on the variances of intensity and angular location estimates for two closely spaced optical targets are derived. Representative results for the estimation performance degradation due to the interfering targets are shown.

Publisher Summary This chapter explains the identification of putative precursors of ovalbumin and ovomucoid messenger rRNAs. In an experiment described in the chapter, specific DNA probes prepared from structural and intervening sequences within the natural ovalbumin gene were used to identify the precursors of ovalbumin mRNA. Nuclear RNA from hormone-stimulated chick oviducts was electrophoresed under denaturing condition followed by transfer to diazobenzyloxymethyl paper, and hybridization to 32p-DNA probes for structural sequence probes to cytoplasmic RNA gave a single low molecular weight band at the expected size of mature ovalbumin mRNA. Hybridization of the same probe to nuclear RNA demonstrated multiple species of RNA that are higher in molecular weight than mature ovalbumin rRNA. The largest molecule has a molecular weight of more than 8000 nucleotides in length, which could accommodate the entire natural ovalbumin gene sequence. These high-molecular-weight species contain RNA complementary to both structural and intervening sequences of the ovalbumin gene and, thus, appear to represent ovalbumin gene transcripts at various processing stages.

The capabilities of the maximum likelihood estimator (MLE) and the maximum entropy method (MEM) in resolving closely spaced optical point targets are compared using Monte Carlo simulation results for three different examples. It is found that the MEM is very sensitive to the noise and that the MLE performs better than the MEM in all examples.

Estrogen (diethylstilbesterol) was administered in vivo to chicks for various time periods. Chromatin was then prepared from oviduct nuclei and assayed for its capacity to support initiation of RNA chain synthesis in vitro in the presence of saturating levels of Escherichia coli RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate:RNA nucleotidyltransferase; EC 2.7.7.6). These same nuclei were also assayed by a [3H]estradiol exchange assay for their endogenous receptor content. The number of available initiation sites for RNA synthesis on chromatin was shown to correlate with the endogenous levels of nuclear estrogen receptor. A decrease in the nuclear concentration of estrogen receptor molecules and the concentration of initiation sites for RNA synthesis occurred during withdrawal of estrogen from previously stimulated chicks. Both parameters declined with a similar half-life. When estrogen was readministered to withdrawn chicks, the number of initiation sites increased 2-fold as early as 30 min and approached a maximal level (3-fold) by 1 hr. During the same period of restimulation with estrogen, the number of estrogen receptor molecules bound to nuclei increased to a maximum at 20 min and then declined at 1 hr to a steady-state level 2-fold higher than the withdrawn chicks. Simultaneous measurements of RNA chain length and RNA chain propagation rate demonstrated that parameters remained relatively constant throughout estrogen withdrawal as well as secondary stimulation. The temporal correlation between changes in the levels of nuclear-bound estrogen receptor and the number of RNA chain initiation sites on chromatin prepared from these same nuclei strongly suggested that the hormone receptor complexes act on chromatin to mediate these changes in genetic transcriptional activity.

Denaturing gel electrophoresis of chick oviduct nuclear RNA reveals multiple species of RNA that are 1.5–5 times larger than ovomucoid mRNA. By analogy with ovalbumin RNA processing, these data suggest that ovomucoid mRNA is derived from a primary transcript that contains intervening sequences.

The transcription of structural and intervening sequences of the chicken ovalbumin gene was studied in nuclei isolated from the oviduct, liver, and spleen of chickens in different states of estrogen simulation. The concentration of transcripts of structural and intervening DNA sequences was determined by hybridizing the newly synthesized [ 3 H]RNA to filters containing cloned ovalbumin cDNA (pOV230) or fragments of the natural ovalbumin gene (pOV2.4 and pOV1.8). Of the RNA synthesized by oviduct nuclei from chickens chronically stimulated with diethylstilbestrol, 0.23% corresponded to ovalbumin mRNA and 0.17% were transcripts of intervening sequences. No detectable ovalbumin mRNA sequences were synthesized by nuclei from spleen and liver. After 60 hr of hormone withdrawal, synthesis of ovalbumin mRNA by oviduct nuclei could not be detected. After readministration of estrogen, a gradual increase in ovalbumin mRNA synthesis was observed which began at 1 hr and reached a plateau by 8 hr. For the intervening sequences, similar kinetics were observed for the initial 4 hr. Previously we had identified multiple species of putative precursors of ovalbumin mRNA in oviduct nuclei from chickens chronically stimulated with diethylstilbestrol. We demonstrate here that withdrawal of diethylstilbestrol resulted in a depletion of high-molecular-weight ovalbumin RNA and of mature ovalbumin mRNA and that readministration of the estrogen induced the nuclear accumulation of both forms of ovalbumin RNA. These findings indicate that: ( i ) a method exists to assay synthesis of hormone-inducible specific eukaryotic [ 3 H]mRNA in vitro; ( ii ) the estrogen-mediated preferential expression of the ovalbumin gene is maintained in isolated oviduct nuclei; ( iii ) after hormone withdrawal, a single injection of diethylstilbestrol induces transcription of ovalbumin structural and intervening sequences, with nuclear accumulation of high-molecular-weight ovalbumin RNA and mature ovalbumin mRNA; and ( iv ) these results are consistent with regulation of ovalbumin mRNA at the level of ovalbumin gene transcription.

To understand the molecular basis of the steroid hormone regulated expression of the ovalbumin gene, we sought to identify and isolate nuclear factors from chicken oviduct which interact specifically with the ovalbumin promoter. Using DNase I footprinting and mobility shift assays, we have defined at least four distinct protein binding sites, OV-150, OV-220, OV-250 and OV-330, in the promoter region between -100 to -400. Binding competition and protein fractionation studies revealed the existence of two distinct proteins, each recognizing two promoter sites: Both OV-330 and OV-250 are recognized by one protein factor which is distinct from the one binding to both OV-220 and OV-150. The location of the DNase I footprints coincides with those of in vivo chromatin hypersensitive sites. The OV-330 site is located in a sequence area required for the repression of the gene in the absence of hormone. The factor binding to OV-330 has been substantially purified and renaturation experiments indicate that the binding activity is associated with a polypeptide(s) of Mr 40K.

We have used a bovine papillomavirus-based vector to generate transgenic mice. Transgenic mice result from either pronuclear or cytoplasmic injections of the vector into fertilized eggs. Of 30 mice generated by microinjection, 27 (90%) contained the vector in its episomal form, at less than one copy per cell. This represents a highly efficient means of gene transfer in which the transgene is in a controlled genetic environment.

Insulin is one of the key peptide hormones in the control of growth and metabolism. The imbalance of insulin action results in diabetes mellitus which has broad impact on the society. Aside from its medical importance, the insulin gene is interesting because it is specifically expressed in the β-cells of the islets of Langerhans in the pancreas, and this tissue-specificity is at the transcriptional level. Therefore, the insulin gene serves as a good model system for studies of gene expression.

The problem of track initiation in the exoatmospheric ballistic missile defense scenario has been studied before, assuming a scanning LWIR sensor. This paper is concerned with the same problem, but under a more difficult sensor configuration, namely, a set of mid-altitude satellite sensors. To handle conditions of high target density and poor observability, a new initiation procedure is used for the iterative-least-square (ILS) filter, and the filter itself is modified to accept a-priori state covariance. The target density is effectively reduced by calling upon an edge tracker initially, which forms track files of edges of the clusters. Track initiation is then accomplished by referencing to those edge track files, assuming that targets in the same cluster travel in parallel. Tracks initiated by two sensors are merged to provide precise state estimates to the extended Kalman filter that is used to carry out the track maintenance task.

Incubation of a HeLa cell fraction termed P1000 with genomic DNA fragments containing portions of the 5'-flanking region of the ovalbumin gene, followed by digestion with exonucleases, shows that this cell fraction contains a protein (or proteins) that binds to the distal promoter of the ovalbumin gene. The protein protects both strands and spans a minimum of 22 bp on the noncoding strand from nucleotides -68 to -90. The 5' border of the protected region on the coding strand is located at nucleotide -81. A similar site on the chick beta-globin gene is also protected by HeLa cell fraction P1000. The exonuclease footprinting methods used to identify the distal promoter-binding protein are more sensitive than the DNaseI footprinting method, and can be used to identify sequence-specific binding proteins in a mixture of DNA binding proteins.

Nuclear matrix was prepared by sequential treatment of oviduct nuclei with Triton X-100, DNase I, and 2 M NaCl. Published procedures were modified such that as many steps as possible were performed at -20 degrees C to minimize endogenous ribonuclease activity. Examination of electron micrographs confirmed the isolation of intact nuclear matrix structures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins in these structures showed an absence of histones and an enrichment of certain nonhistone proteins. RNA was isolated from the nuclear matrix preparations and subjected to denaturing gel electrophoresis. Gels were analyzed by ethidium bromide staining and by hybridization of Northern blots to cloned DNA probes for ovalbumin, ovomucoid, 5.8S ribosomal RNA, and U1 RNA. All of the precursors to ovalbumin and ovomucoid mRNAs (including various splicing intermediates) and all of the precursors to ribosomal RNA were associated exclusively with the nuclear matrix fraction. By contrast, mature ovalbumin and ovomucoid mRNAs were distributed between matrix and nonmatrix fractions. These observations were further supported by quantitative hybridization analysis of the RNA in nuclear and matrix fractions. It was found that less than 50% of the mature message of intact nuclei was recovered in the matrix, while most significantly, over 95% of the mRNA precursors remained associated with the matrix. Finally, mature ribosomal RNAs and virtually all of the small nuclear RNAs (including U1 RNA) were also distributed between matrix and nonmatrix fractions. Our results suggest that all precursor RNAs (be they precursors to mRNA or rRNA) are exclusively associated with the nuclear matrix and support the notion that the nuclear matrix may be the structural site for RNA processing within the nuclei of eucaryotic cells.

The natural gene for a steroid inducible 108K heat shock protein has been isolated from a lambda genomic library prepared from hen oviduct tissue. Genomic DNA blots indicate that it exists as a single copy gene in the chick oviduct haploid genome. The 9.9 kilobase gene codes for a messenger RNA of 2733bp (21) and is split into 18 exons as established by sequence comparison of cDNA and genomic clones. The 3' end of the gene contains a repetitive element which shares homology with the CR1 family of repeats. The first exon contains both the untranslated leader and coding regions of the gene. The promoter region is rich in G + C residues (70%) and the dinucleotide CG. This 5' flanking segment contains bases similar both in sequence and location to the Goldberg-Hogness TATA homology and consensus sequence CCAAT. A consensus sequence located upstream of steroid hormone responsive chicken genes is found at -267 and on a reverse orientation at -593. The structure of this gene is of interest since the presence of introns in heat shock genes is rare in any species examined to date. Furthermore, this gene lacks the previously described heat shock promoter consensus sequence (C-GAA-TTC-G) present in other species.

Publisher Summary This chapter discusses the regulation of expression of the chicken ovalbumin gene by steroid hormones. Upon entering the cell, steroid hormones are initially bound to specific cytoplasmic protein receptors. The hormone–receptor complex undergoes activation and translocates from the cytoplasm into the nucleus. In the nuclear compartment, the hormone–receptor complex binds to acceptor sites on the target cell chromatin. This is followed by the activation of specific genes resulting in the appearance of new species of RNA. The progesterone receptor of chick oviduct is a dimer composed of A and B subunits. This subunit structure has been confirmed by the use of a reversible cross-linking reagent that will cross-link the native dimer. After extraction and partial purification, the dimer can be dissociated, releasing equimolar amounts of the A and B proteins. The A protein has a molecular weight of 79,000, and that of the B protein is 117,000. Evidence indicates that the entire gene of ovalbumin gene is transcribed as a unit into a primary transcript of RNA that appears to be subsequently processed into mature mRNA by the reactions of precise cleavage and ligation. Thus, an abundant amount of intracistronic DNA will never be expressed in the phenotype as proteins. As the cell is under environmental pressure to construct proteins (enzymes) with a particular set of characteristics, the cell could have been encouraged to splice together new polypeptides via the assembly of various segments of DNA into a gene region.

Analysis of the functional properties of two naturally occurring chicken progesterone receptors (cPR) has allowed us to begin to examine the interaction of steroid receptors with transcription factors. The cPR A and B proteins differ by an additional 128 amino acids located at the N-terminus of the B protein. These proteins are functionally distinct in terms of their ability to activate specific traget genes. The N-terminal region of the cPR B protein is an acidic domain which acts as a promoter specific transcriptional regulating domain when transferred to a heterologous receptor. The regulatory function of this domain is independent of the DNA binding specificity of the receptor and appears to reflect modulation of receptor interaction with transcription factors. The estrogen and progesterone receptors appear to interact with common transcription factors. Competition for common transcription factors by these proteins does not require DNA binding.

cDNA clones encoding a protein that copurifies with the progesterone receptor B subunit but does not bind progesterone have been described [Kulomaa, M. S., Weigel, N. L., Kleinsek, D. A., Beattie, W. G., Conneely, O. M., March, C., Zarucki-Schulz, T., Schrader, W. T., & O'Malley, B. W. (1986) Biochemistry (preceding paper in this issue)]. A full-length sequence for these clones was derived and was found to encode a protein that is structurally unrelated to the progesterone receptor but that contains significant homologies to the previously described heat shock proteins hsp90 of yeast and hsp83a of Drosophila melanogaster. In this paper it is shown that this protein is indeed a heat shock protein. Though the apparent molecular weight of the protein is 108,000 on sodium dodecyl sulfate-polyacrylamide gels, the molecular weight of the polypeptide backbone is 92,000. The steady-state level of gene transcripts as well as the level of protein is inducible by heat shock, but the gene is constitutively expressed in a number of tissues. A previously undescribed heat shock protein of molecular weight 78,000 in these preparations is also reported.

A study was made of the function of the intervening sequences in the ovalbumin gene, Radioactively labeled DNA probes for the intervening sequences were prepared and RNA's were isolated from whole cells, nuclei, and polysomes of estrogen-stimulated chick oviducts. The concentrations of messenger RNA (mRNA) transcripts from ovalbumin structural sequences (mRNAov) and transcripts corresponding to intervening sequences were then estimated by hybridization to cloned DNA probes. Oviduct tissue contains approximately 58,000 molecules of mRNAov sequences per tubular gland cell and most of these sequences are present in the cytoplasm. In contrast, there are 200 to 300 molecules of RNA per cell which are transcribed from the intervening sequences of the natural ovalbumin gene and almost all of these are found in the nucleus. The difference in distribution of structural and intervening sequence transcripts suggests that, unlike mature mRNA, the intervening sequences are not preferentially transported to cytoplasmic polysomes.

Publisher Summary This chapter focuses on the ovomucoid gene organization, structure, and regulation. The molecular mechanism by which steroid hormones regulate specific gene expression has been an area of acute interest. One attractive model system for studying this hormonal regulation has been the hen oviduct. Administration of estrogen to the newborn chick stimulates oviduct growth and differentiation and results in the appearance of a number of new specific intracellular proteins. The synthesis of one of these proteins, ovalbumin, has been studied. Ovalbumin mRNA has been purified and a full-length dsDNA copy synthesized and cloned in a bacterial plasmid. Moreover, ovalbumin genomic DNA sequences have been isolated from restriction enzyme digests of hen DNA and cloned. The chapter discusses the cloning of the ovomucoid structural gene sequence. It also describes the synthesis and cloning of a complementary DNA copy and identification of an ovomucoid structural gene clone And discusses a partial restriction map of pOM100.

A steroid hormone responsive element (GRE/PRE), sufficient to confer glucocorticoid and progesterone inducibility when linked to a reporter gene, was used in band-shift assays to examine its molecular interactions with steroid hormone receptors. Both progesterone and glucocorticoid receptors bound directly and specifically to the GRE/PRE. The purine contact sites for both form A and form B chicken progesterone receptor, as well as those for rat glucocorticoid receptor, are identical. A peptide fragment produced in bacteria that primarily contain the DNA binding domain of the glucocorticoid receptor binds first to the TGTTCT half-site of the GRE/PRE, and a second molecule binds subsequently to the TGTACA (half-site) of the GRE/PRE in a cooperative manner. Utilizing the peptide fragment and the protein A-linked fragment, we demonstrated that the receptor interacts with its cognate enhancer as a dimer.

The sequence organization of the structural ovalbumin gene and flanking sequences in native chick DNA was studied by restriction mapping and filter hybridization using a nick-translated probe generated from p0V230, a recombinant plasmid which contains a full-length ovalbumin DNA synthesized from ovalbumin mRNA. The structural sequences of the ovalbumin gene in native chick DNA were found to be non-contiguous because at least two restriction endonucleases that do not cut the structural sequence do cleave the natural gene into multiple fragments by cleaving within non-structural sequences interspersed between the structural sequences. The observation that all ovalbumin DNA-containing sequences were contained within a single DNA fragment generated by Bam HI digestion of total chick DNA has allowed the construction of an inclusive restriction map of the natural ovalbumin gene which contains at least two “insert sequences”. Both “insert sequences” were located within the peptide-coding regions of the gene and the sizes of these “insert sequences” were estimated to be approximately 1.0 and 1.5 Kb, respectively. The same amazing ovalbumin gene organization is present in chick liver, oviduct and embryonic DNA. Pure single-stranded hybridization probes to each of the separate regions of the ovalbumin gene were prepared and hybridized to total chick DNA and oviduct nuclear RNA. Results indicate that transcription of the separated structural regions are coordinately regulated by estrogen.

To study the induction of mRNA ov in chick oviduct tissue, two experimental designs were developed: oviduct tissue incubated in vitro with hormone, and an in vivo system involving hormone injection into the lumen of anesthetized chicks. The magnitude of hormone response in oviduct tissue suspension was shown to depend on the conditions of the incubation medium and on the previous hormonal treatment of the chicken. When animals were withdrawn from estrogen treatment (48–72 h), restimulation of oviduct minces with 10 −8 M estradiol in vitro induced-rapidly the synthesis of mRNA ov . The rate of synthesis reached its peak in the first two hours of incubation, when approximately 0.2% of the mass of the newly synthesized RNA was mRNA ov . A marked decrease in the level of mRNA ov synthesis and a gradual appearance of a lag period was observed when the estrogen withdrawal time was extended beyond 86 h. A nuclear precursor to ovalbumin mRNA could be shown to be processed into mature mRNA ov in this oviduct tissue suspension system. In vivo experiments were performed in chickens after various intervals of time following hormone withdrawal (2–13 days). Estradiol (10 −8 M) was injected into the oviduct lumen of anesthetized chicks. Within two hours a nearly maximal rate of mRNA ov synthesis was observed. These two systems have proven to be efficient for the assay of the estrogen-mediated induction of mRNA ov synthesis and serve to support the hypothesis that in the chick oviduct system, estrogen regulation of gene expression is primarily at the transcriptional level.

The DNA-dependent RNA polymerase present in the mitochondria of Saccharomyces cerevisiae has been solubilized using a 0.5 M KCI solution, and the soluble enzyme has been purified. Two forms of mitochondrial enzyme were obtained; they differ in their template specificity and metal-ion dependency. The mitochondrial RNA polymerase also differs from enzyme obtained from the nucleus with respect to antibiotic sensitivity and template specificity. Only the nuclear enzyme is sensitive to α-amanitin inhibition. The relative activities of the isolated nuclear and mitochondrial polymerases toward their homologous DNAs are consistent with their in vivo functions. The possibilities of bacterial- and nuclear-enzyme contamination of the mitochondrial enzyme preparation have been ruled out. RNA polymerase activity in two petite mutants has been studied. Isolated mitochondria from a petite mutant with no detectable mitochondrial DNA has greatly diminished mitochondrial DNA-dependent RNA polymerase activity, while a petite mutant with only a small change in mitochondrial DNA base composition has normal amounts of enzyme.

Ethidium bromide is known to be a powerful mutagen for the induction of cytoplasmically inherited petite mutations in yeast. The effect of ethidium bromide on the degree of suppressiveness of the induced mutants as a function of exposure time is described. The mitochondrial DNA of 20 ethidium bromide-induced petite mutants has been studied to determine its absence or presence and its buoyant density. Ten mutants, in which we were not able to detect any mitochondrial DNA, were neutral petites. The 10 remaining mutants with mitochondrial DNA simultaneously showed a measurable degree of suppressiveness. It was not possible to correlate the buoyant density of the mutant mitochondrial DNA with the degree of suppressiveness.

In this paper, we investigate the wireless network deployment problem, which seeks the best deployment of a given limited number of wireless routers. We find that many goals for network deployment, such as maximizing the number of covered users, the size of the coverage area, or the total throughput of the network, can be modeled with a submodular set function. Specifically, given a set of routers, the goal is to find a set of locations $S$ , each of which is equipped with a router, such that $S$ maximizes a predefined submodular set function. However, this deployment problem is more difficult than the traditional maximum submodular set function problem, e.g., the maximum coverage problem, because it requires all the deployed routers to form a connected network. In addition, deploying a router in different locations might consume different costs. To address these challenges, this paper introduces two approximation algorithms, one for homogeneous deployment cost scenarios and the other for heterogeneous deployment cost scenarios. Our simulations, using synthetic data and real traces of census in Taipei, Taiwan, show that the proposed algorithms achieve better performances than other heuristics.

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) belongs to the steroid/thyroid hormone receptor superfamily. Extensive evidence has indicated that COUP-TFII plays a critical and indispensable role in cell-fate specification, organogenesis, angiogenesis, and metabolism as well as in a variety of diseases. Recent studies obtained from genetically engineered mouse models (GEM) and patient specimen analysis indicate that COUP-TFII is also important for tumor progression and metastasis. In this article, we will comprehensively review the oncogenic roles of COUP-TFII within the tumor microenvironment and tumor cells and delineate the mechanism by which COUP-TFII contributes to tumorigenesis. The applicability of current data to our understanding of the role of COUP-TFII in cancer and the potential therapeutic implications will also be discussed.