@article {49757, title = {Evolutionarily conserved network properties of intrinsically disordered proteins.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0126729}, abstract = {

BACKGROUND: Intrinsically disordered proteins (IDPs) lack a stable tertiary structure in isolation. Remarkably, however, a substantial portion of IDPs undergo disorder-to-order transitions upon binding to their cognate partners. Structural flexibility and binding plasticity enable IDPs to interact with a broad range of partners. However, the broader network properties that could provide additional insights into the functional role of IDPs are not known.

RESULTS: Here, we report the first comprehensive survey of network properties of IDP-induced sub-networks in multiple species from yeast to human. Our results show that IDPs exhibit greater-than-expected modularity and are connected to the rest of the protein interaction network (PIN) via proteins that exhibit the highest betweenness centrality and connect to fewer-than-expected IDP communities, suggesting that they form critical communication links from IDP modules to the rest of the PIN. Moreover, we found that IDPs are enriched at the top level of regulatory hierarchy.

CONCLUSION: Overall, our analyses reveal coherent and remarkably conserved IDP-centric network properties, namely, modularity in IDP-induced network and a layer of critical nodes connecting IDPs with the rest of the PIN.

}, keywords = {Animals, Cluster Analysis, Databases, Protein, Drosophila, Drosophila Proteins, Evolution, Molecular, HUMANS, Intrinsically Disordered Proteins, Metabolic Networks and Pathways, Mice, Osmotic Pressure, Protein Interaction Maps, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins}, issn = {1932-6203}, doi = {10.1371/journal.pone.0126729}, author = {Rangarajan, Nivedita and Kulkarni, Prakash and Hannenhalli, Sridhar} } @article {38584, title = {CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation}, journal = {Nucleic Acids ResNucleic Acids ResNucleic Acids Res}, volume = {42}, number = {2}, year = {2014}, note = {Plasschaert, Robert N
Vigneau, Sebastien
Tempera, Italo
Gupta, Ravi
Maksimoska, Jasna
Everett, Logan
Davuluri, Ramana
Mamorstein, Ronen
Lieberman, Paul M
Schultz, David
Hannenhalli, Sridhar
Bartolomei, Marisa S
eng
K99AI099153/AI/NIAID NIH HHS/
P30 CA10815/CA/NCI NIH HHS/
R01 CA140652/CA/NCI NIH HHS/
R01-GM052880/GM/NIGMS NIH HHS/
R01CA140652/CA/NCI NIH HHS/
R01GM085226/GM/NIGMS NIH HHS/
R01HD042026/HD/NICHD NIH HHS/
T32GM008216/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov{\textquoteright}t
England
2013/10/15 06:00
Nucleic Acids Res. 2014 Jan;42(2):774-89. doi: 10.1093/nar/gkt910. Epub 2013 Oct 10.}, month = {Jan}, pages = {774-89}, abstract = {CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF{\textquoteright}s binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site.}, keywords = {*Gene Expression Regulation, *Regulatory Elements, Transcriptional, Animals, Binding Sites, Cell Differentiation/*genetics, Cells, Cultured, Embryonic Stem Cells/cytology/*metabolism, Mice, Nucleotide Motifs, Protein Binding, Repressor Proteins/*metabolism}, isbn = {1362-4962 (Electronic)
0305-1048 (Linking)}, author = {Plasschaert, R. N. and Vigneau, S. and Tempera, I. and Gupta, R. and Maksimoska, J. and Everett, L. and Davuluri, R. and Mamorstein, R. and Lieberman, P. M. and Schultz, D. and Sridhar Hannenhalli and Bartolomei, M. S.} } @article {49740, title = {Global secretome analysis identifies novel mediators of bone metastasis.}, journal = {Cell Res}, volume = {22}, year = {2012}, month = {2012 Sep}, pages = {1339-55}, abstract = {

Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

}, keywords = {Animals, Biomarkers, Tumor, Bone Neoplasms, Cell Line, Tumor, Collagen Type VI, Computational Biology, HUMANS, Mass Spectrometry, Mice, Neoplasms, Plasminogen Activators, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, Proteome, proteomics, Salivary Cystatins}, issn = {1748-7838}, doi = {10.1038/cr.2012.89}, author = {Blanco, Mario Andres and LeRoy, Gary and Khan, Zia and Ale{\v c}kovi{\'c}, Ma{\v s}a and Zee, Barry M and Garcia, Benjamin A and Kang, Yibin} } @article {49746, title = {Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.}, journal = {Nat Med}, volume = {17}, year = {2011}, month = {2011 Sep}, pages = {1101-8}, abstract = {

Although the role of miR-200s in regulating E-cadherin expression and epithelial-to-mesenchymal transition is well established, their influence on metastatic colonization remains controversial. Here we have used clinical and experimental models of breast cancer metastasis to discover a pro-metastatic role of miR-200s that goes beyond their regulation of E-cadherin and epithelial phenotype. Overexpression of miR-200s is associated with increased risk of metastasis in breast cancer and promotes metastatic colonization in mouse models, phenotypes that cannot be recapitulated by E-cadherin expression alone. Genomic and proteomic analyses revealed global shifts in gene expression upon miR-200 overexpression toward that of highly metastatic cells. miR-200s promote metastatic colonization partly through direct targeting of Sec23a, which mediates secretion of metastasis-suppressive proteins, including Igfbp4 and Tinagl1, as validated by functional and clinical correlation studies. Overall, these findings suggest a pleiotropic role of miR-200s in promoting metastatic colonization by influencing E-cadherin-dependent epithelial traits and Sec23a-mediated tumor cell secretome.

}, keywords = {Animals, Cadherins, Cell Line, Tumor, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HUMANS, Mass Spectrometry, Mice, Mice, Inbred BALB C, Microarray Analysis, MicroRNAs, Neoplasm Metastasis, Statistics, Nonparametric, Vesicular Transport Proteins}, issn = {1546-170X}, doi = {10.1038/nm.2401}, author = {Korpal, Manav and Ell, Brian J and Buffa, Francesca M and Ibrahim, Toni and Blanco, Mario A and Celi{\`a}-Terrassa, Toni and Mercatali, Laura and Khan, Zia and Goodarzi, Hani and Hua, Yuling and Wei, Yong and Hu, Guohong and Garcia, Benjamin A and Ragoussis, Jiannis and Amadori, Dino and Harris, Adrian L and Kang, Yibin} } @article {49727, title = {Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.}, journal = {Nature}, volume = {477}, year = {2011}, month = {2011 Sep 8}, pages = {225-8}, abstract = {

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.

}, keywords = {Animals, Bilirubin, Cell Line, Cells, Cultured, Citric Acid Cycle, Computer simulation, Fumarate Hydratase, Fumarates, Genes, Lethal, Genes, Tumor Suppressor, Glutamine, Heme, Heme Oxygenase (Decyclizing), Kidney Neoplasms, Leiomyomatosis, Mice, Mitochondria, Mutation, NAD, Neoplastic Syndromes, Hereditary, Skin Neoplasms, Uterine Neoplasms}, issn = {1476-4687}, doi = {10.1038/nature10363}, author = {Frezza, Christian and Zheng, Liang and Folger, Ori and Rajagopalan, Kartik N and MacKenzie, Elaine D and Jerby, Livnat and Micaroni, Massimo and Chaneton, Barbara and Adam, Julie and Hedley, Ann and Kalna, Gabriela and Tomlinson, Ian P M and Pollard, Patrick J and Watson, Dave G and Deberardinis, Ralph J and Shlomi, Tomer and Ruppin, Eytan and Gottlieb, Eyal} } @article {49747, title = {Protein quantification across hundreds of experimental conditions.}, journal = {Proc Natl Acad Sci U S A}, volume = {106}, year = {2009}, month = {2009 Sep 15}, pages = {15544-8}, abstract = {

Quantitative studies of protein abundance rarely span more than a small number of experimental conditions and replicates. In contrast, quantitative studies of transcript abundance often span hundreds of experimental conditions and replicates. This situation exists, in part, because extracting quantitative data from large proteomics datasets is significantly more difficult than reading quantitative data from a gene expression microarray. To address this problem, we introduce two algorithmic advances in the processing of quantitative proteomics data. First, we use space-partitioning data structures to handle the large size of these datasets. Second, we introduce techniques that combine graph-theoretic algorithms with space-partitioning data structures to collect relative protein abundance data across hundreds of experimental conditions and replicates. We validate these algorithmic techniques by analyzing several datasets and computing both internal and external measures of quantification accuracy. We demonstrate the scalability of these techniques by applying them to a large dataset that comprises a total of 472 experimental conditions and replicates.

}, keywords = {algorithms, Animals, Automatic Data Processing, Chromatography, Liquid, Databases, Factual, Fungal Proteins, HUMANS, Isotopes, Mice, Proteins, proteomics, Tandem Mass Spectrometry}, issn = {1091-6490}, doi = {10.1073/pnas.0904100106}, author = {Khan, Zia and Bloom, Joshua S and Garcia, Benjamin A and Singh, Mona and Kruglyak, Leonid} } @article {49643, title = {Schistosoma mansoni: Microarray analysis of gene expression induced by host sex.}, journal = {Exp Parasitol}, volume = {120}, year = {2008}, month = {2008 Dec}, pages = {357-63}, abstract = {

Schistosoma mansoni is a digenetic trematode and a human parasite responsible for high social and economic impact. Although some authors have studied the effect of host hormones on parasites, not much is known about the effects of host sex on gene expression in Schistosomes. In order to study gene transcripts associated with the host sex, we compared the gene expression profiles of both male and female unisexual adult S. mansoni parasites raised on either male or female hosts, using DNA microarrays. Our results show that host sex caused differential expression of at least 11 genes in female parasites and of 134 in male parasites. Of the differentially expressed genes in female worms, 10 were preferentially expressed in female worms from male mice, while of the 134 differentially expressed genes in male parasites, 79 (59\%) were preferentially expressed in worms from female mice. Further investigation of the role of each of those genes will help understand better their importance in the pathogenesis of Schistosomiasis.

}, keywords = {Animals, Biomphalaria, Female, Gene expression, Host-Parasite Interactions, Male, Mice, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, RNA, Helminth, Schistosoma mansoni, Schistosomiasis mansoni, Sex Factors}, issn = {1090-2449}, doi = {10.1016/j.exppara.2008.09.005}, author = {Waisberg, M and Lobo, F P and Cerqueira, G C and Passos, L K J and Carvalho, O S and El-Sayed, N M and Franco, G R} } @article {38578, title = {X-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of the haloacid dehalogenase superfamily}, journal = {BiochemistryBiochemistry}, volume = {43}, year = {2004}, note = {http://www.ncbi.nlm.nih.gov/pubmed/15461449?dopt=Abstract}, type = {10.1021/bi0490688}, abstract = {The haloacid dehalogenase (HAD) superfamily is comprised of structurally homologous enzymes that share several conserved sequence motifs (loops I-IV) in their active site. The majority of HAD members are phosphohydrolases and may be divided into three subclasses depending on domain organization. In classes I and II, a mobile "cap" domain reorients upon substrate binding, closing the active site to bulk solvent. Members of the third class lack this additional domain. Herein, we report the 1.9 A X-ray crystal structures of a member of the third subclass, magnesium-dependent phosphatase-1 (MDP-1) both in its unliganded form and with the product analogue, tungstate, bound to the active site. The secondary structure of MDP-1 is similar to that of the "core" domain of other type I and type II HAD members with the addition of a small, 28-amino acid insert that does not close down to exclude bulk solvent in the presence of ligand. In addition, the monomeric oligomeric state of MDP-1 does not allow the participation of a second subunit in the formation and solvent protection of the active site. The binding sites for the phosphate portion of the substrate and Mg(II) cofactor are also similar to those of other HAD members, with all previously observed contacts conserved. Unlike other subclass III HAD members, MDP-1 appears to be equally able to dephosphorylate phosphotyrosine and closed-ring phosphosugars. Modeling of possible substrates in the active site of MDP-1 reveals very few potential interactions with the substrate leaving group. The mapping of conserved residues in sequences of MDP-1 from different eukaryotic organisms reveals that they colocalize to a large region on the surface of the protein outside the active site. This observation combined with the modeling studies suggests that the target of MDP-1 is most likely a phosphotyrosine in an unknown protein rather than a small sugar-based substrate.}, keywords = {Amino Acid Sequence, Animals, Binding Sites, Crystallography, X-Ray, HUMANS, Hydrogen-Ion Concentration, Hydrolases, Magnesium, Mice, Models, Molecular, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphotyrosine, Protein Phosphatase 1, Protein Structure, Quaternary, Protein Structure, Tertiary, sequence alignment, Solvents, Substrate Specificity}, author = {Peisach, Ezra and J. Selengut and Dunaway-Mariano, Debra and Allen, Karen N.} } @proceedings {38218, title = {Dynamic querying for pattern identification in microarray and genomic data}, volume = {3}, year = {2003}, month = {2003}, publisher = {IEEE}, type = {10.1109/ICME.2003.1221346}, abstract = {Data sets involving linear ordered sequences are a recurring theme in bioinformatics. Dynamic query tools that support exploration of these data sets can be useful for identifying patterns of interest. This paper describes the use of one such tool - timesearcher - to interactively explore linear sequence data sets taken from two bioinformatics problems. Microarray time course data sets involve expression levels for large numbers of genes over multiple time points. Timesearcher can be used to interactively search these data sets for genes with expression profiles of interest. The occurrence frequencies of short sequences of DNA in aligned exons can be used to identify sequences that play a role in the pre-mRNA splicing. Timesearcher can be used to search these data sets for candidate splicing signals.}, keywords = {Bioinformatics, data sets, Displays, dynamic querying, expression profiles, Frequency, Gene expression, genes, Genetics, genomic data, Genomics, linear ordered sequences, macromolecules, medical signal processing, Mice, Microarray, pattern identification, pattern recognition, premRNA splicing, Query processing, sequences, Signal processing, splicing, TimeSearcher}, isbn = {0-7803-7965-9}, author = {Hochheiser, H. and Baehrecke, E. H. and Stephen M. Mount and Shneiderman, Ben} } @article {38536, title = {The transcription factor Eyes absent is a protein tyrosine phosphatase}, journal = {NatureNature}, volume = {426}, year = {2003}, note = {http://www.ncbi.nlm.nih.gov/pubmed/14628053?dopt=Abstract}, type = {10.1038/nature02097}, abstract = {Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Antibodies, Phospho-Specific, Drosophila melanogaster, Drosophila Proteins, Embryonic Induction, eye, Eye Proteins, Gene Expression Regulation, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Phosphorylation, Protein Conformation, Protein Tyrosine Phosphatases, Substrate Specificity, Transcription Factors}, author = {Tootle, Tina L. and Silver, Serena J. and Davies, Erin L. and Newman, Victoria and Latek, Robert R. and Mills, Ishara A. and J. Selengut and Parlikar, Beth E. W. and Rebay, Ilaria} } @article {38368, title = {MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases}, journal = {BiochemistryBiochemistry}, volume = {40}, year = {2001}, note = {http://www.ncbi.nlm.nih.gov/pubmed/11601995?dopt=Abstract}, abstract = {MDP-1 is a eukaryotic magnesium-dependent acid phosphatase with little sequence homology to previously characterized phosphatases. The presence of a conserved motif (Asp-X-Asp-X-Thr) in the N terminus of MDP-1 suggested a relationship to the haloacid dehalogenase (HAD) superfamily, which contains a number of magnesium-dependent acid phosphatases. These phosphatases utilize an aspartate nucleophile and contain a number of conserved active-site residues and hydrophobic patches, which can be plausibly aligned with conserved residues in MDP-1. Seven site-specific point mutants of MDP-1 were produced by modifying the catalytic aspartate, serine, and lysine residues to asparagine or glutamate, alanine, and arginine, respectively. The activity of these mutants confirms the assignment of MDP-1 as a member of the HAD superfamily. Detailed comparison of the sequence of the 15 MDP-1 sequences from various organisms with other HAD superfamily sequences suggests that MDP-1 is not closely related to any particular member of the superfamily. The crystal structures of several HAD family enzymes identify a domain proximal to the active site responsible for important interactions with low molecular weight substrates. The absence of this domain or any other that might perform the same function in MDP-1 suggests an "open" active site capable of interactions with large substrates such as proteins. This suggestion was experimentally confirmed by demonstration that MDP-1 is competent to catalyze the dephosphorylation of tyrosine-phosphorylated proteins.}, keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Aspartic Acid, Catalytic Domain, HUMANS, Hydrolases, Mice, Molecular Sequence Data, Multigene Family, Mutagenesis, Site-Directed, Phosphoprotein Phosphatases, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Rats, Saccharomyces cerevisiae, sequence alignment, Sequence Homology, Amino Acid}, author = {J. Selengut} } @article {38369, title = {MDP-1: A novel eukaryotic magnesium-dependent phosphatase}, journal = {BiochemistryBiochemistry}, volume = {39}, year = {2000}, note = {http://www.ncbi.nlm.nih.gov/pubmed/10889041?dopt=Abstract}, abstract = {We report here the purification, cloning, expression, and characterization of a novel phosphatase, MDP-1. In the course of investigating the reported acid phosphatase activity of carbonic anhydrase III preparations, several discrete phosphatases were discerned. One of these, a magnesium-dependent species of 18.6 kDa, was purified to homogeneity and yielded several peptide sequences from which the parent gene was identified by database searching. Although orthologous genes were identified in fungi and plants as well as mammalian species, there was no apparent homology to any known family of phosphatases. The enzyme was expressed in Escherichia coli with a fusion tag and purified by affinity methods. The recombinant enzyme showed magnesium-dependent acid phosphatase activity comparable to the originally isolated rabbit protein. The enzyme catalyzes the rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or phosphothreonine is considerable, but the enzyme did not show activity toward five phosphotyrosine-containing peptides. None of the various substrates assayed (including various nucleotide, sugar, amino acid and peptide phosphates, phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM, and many showed negligible rates of hydrolysis. The enzyme is inhibited by vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest that the enzymatic mechanism is not dependent on cysteine, histidine, or nonmagnesium metal ions. In recognition of these observations, the enzyme has been given the name magnesium-dependent phosphatase-1 (MDP-1).}, keywords = {Amino Acid Sequence, Animals, Catalysis, Cations, Chromatography, Affinity, Cloning, Molecular, Cysteine, Enzyme Inhibitors, Histidine, Hydrogen-Ion Concentration, Magnesium, Mice, Molecular Sequence Data, Phosphoprotein Phosphatases, Protein Phosphatase 1, Rabbits, Sequence Analysis, Protein, Sequence Homology, Amino Acid, Substrate Specificity}, author = {J. Selengut and Levine, R. L.} } @article {49716, title = {Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis.}, journal = {Cold Spring Harb Symp Quant Biol}, volume = {47 Pt 2}, year = {1983}, month = {1983}, pages = {893-900}, keywords = {Animals, Base Sequence, HeLa Cells, HUMANS, Mice, Molecular Weight, Nucleic Acid Conformation, Nucleic Acid Hybridization, Nucleoproteins, Ribonucleoproteins, Ribonucleoproteins, Small Nuclear, RNA Polymerase III, Transcription, Genetic}, issn = {0091-7451}, author = {Steitz, J A and Wolin, S L and Rinke, J and Pettersson, I and Mount, S M and Lerner, E A and Hinterberger, M and Gottlieb, E} } @article {49628, title = {Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling.}, journal = {J Exp Med}, volume = {143}, year = {1976}, month = {1976 Feb 1}, pages = {348-59}, abstract = {

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.

}, keywords = {Animals, Binding Sites, Antibody, Blastocyst, Cell Differentiation, Cell Membrane, Embryo Implantation, Embryonic Development, Epitopes, Female, Histocompatibility Antigens, HLA Antigens, Horseradish Peroxidase, Mice, Mice, Inbred Strains, Pregnancy, Pregnancy, Animal, Trophoblasts}, issn = {0022-1007}, author = {Searle, R F and Sellens, M H and Elson, J and Jenkinson, E J and Billington, W D} }