The expression of intracisternal A particle genes in the preimplantation mouse embryo

Poznanski, Ann; Calarco, Patricia G.

doi:10.1016/0012-1606(91)90077-g

Cited by 47 publications

(25 citation statements)

References 58 publications

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“…Thus, the limited amount of t-PA cDNAs in these libraries is qualitatively and quantitatively consistent with previous information on transcription of this gene product. The levels of highly expressed transcripts such as those of the intracisternal A-type particles (IAP; Lueders and Kuff 1980;Mietz et al 1987) and B1/B2 repeat sequences (Kramerov et al 1979;Krayev et al 1980) have been analyzed previously in total embryonic RNA (Pik6 et al 1984;Taylor and Pik6 1987;Poznanski and Calarco 1991). We find that 0.035% of the clones in the egg library hybridized with an IAP probe (Pik6 et al 1984) or, by calculation, 5950 transcripts in the unfertilized egg are IAP.…”

Section: Purity and Representation Of Cdna Librariesmentioning

confidence: 70%

Gene expression during preimplantation mouse development.

Rothstein¹,

Johnson²,

DeLoia³

et al. 1992

Genes Dev.

154

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To develop a resource for the identification and isolation of genes expressed in the early mammalian embryo, large and representative cDNA libraries were constructed from unfertilized eggs, and two-cell, eight-cell, and blastocyst-stage mouse embryos. Using these libraries, we now report the first stages at which the cytokines interleukin (IL)-6, IL-I[3, and interferon (IFN)-7 are transcribed in the developing embryo and the presence of IL-7 transcripts in the unfertilized egg. Transcripts for IL-I~, -2, -3, -4, or -5 were not detected at these stages. To identify novel genes expressed on activation of the embryonic genome, the egg and eight-cell stage-specific cDNA libraries were subtracted from the two-cell library, yielding a specialized cDNA library enriched for transcripts expressed at the two-cell stage. Sequence and Southern blot analysis of several of these cDNAs expressed predominantly at the two-cell stage of embryogenesis revealed them to be from novel genes, thereby providing the first molecular tools with which to approach the study of gene expression in the early mammalian embryo.

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Section: Purity and Representation Of Cdna Librariesmentioning

confidence: 70%

Gene expression during preimplantation mouse development.

Rothstein¹,

Johnson²,

DeLoia³

et al. 1992

Genes Dev.

154

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“…11,12 Moreover, several findings suggest that endogenous RTcoding genes may be involved in the regulation of cell proliferation and differentiation. 8,13 Indeed, endogenous RT is encoded by retro-transposable elements, such as LINE1, and endogenous retroviruses, 14 and its expression is highly upregulated in embryonic tissues and undifferentiated cells [15][16][17] as well as in tumors, 18,19 whereas it is silenced in differentiated, nonpathological tissues. Consistently, the silencing of RT-encoding LINE-1 elements by RNA interference or the pharmacological inhibition of endogenous RT activity results in a reversible decrease in the rate of cell growth and in the induction of cell differentiation in several human tumor cell lines such as breast, colon, lung, prostate, thyroid carcinoma and melanoma cells.…”

Section: Cd45ramentioning

confidence: 99%

Reverse transcriptase inhibitors induce cell differentiation and enhance the immunogenic phenotype in human renal clear‐cell carcinoma

Landriscina¹,

Altamura²,

Roca³

et al. 2008

Intl Journal of Cancer

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Reverse transcriptase (RT) inhibitors are emerging as a novel class of anticancer differentiating agents, active in several human tumor cell models, such as melanoma and prostate, thyroid and colon carcinoma. Indeed, much evidence suggests that they may act by inhibiting endogenous RT, a gene highly expressed in undifferentiated and transformed cells. We therefore evaluated whether endogenous RT may represent a new molecular target in the treatment of human renal clear-cell carcinoma, a neoplasm with very low sensitivity to standard pharmacological therapies. Efavirenz and nevirapine, 2 non-nucleosidic RT inhibitors commonly used in HIV patients, either induced a reversible downregulation of cell proliferation or enhanced cell differentiation in primary cultures of human renal carcinoma cells characterized by high levels of endogenous RT activity. Both agents upregulated the expression of the vitamin D receptor and calbindin 28k genes, which are constitutively expressed in renal tubular cells, and induced vitamin D signaling by enhancing the ability of tumor cells to upregulate the vitamin D-dependent gene, CYP24. Furthermore, efavirenz-and nevirapine-differentiated tumor cells exhibited an immunogenic phenotype with an increased expression of HLA-I and CD40 antigens and an enhanced ability to elicit a specific T-cell response in mixed lymphocyte/tumor-cell cultures. Indeed, renal carcinoma cells exposed to efavirenz induced a CD8 1 CCR7-CD45RA 2 effector memory T-cell phenotype, whereas untreated RCC cells induced a CD8 1 CCR7 1 CD45RA 2 central memory T-cell phenotype. These data suggest that RT inhibitors may be a novel tool in the treatment of human renal clear-cell carcinoma, potentially able to enhance the immunogenic potential of tumor cell. ' 2008 Wiley-Liss, Inc.Key words: reverse transcriptase; renal cell carcinoma; differentiation; vitamin D receptor; immune response Renal clear-cell carcinoma represents 75-80% of all human renal epithelial neoplasms, and its incidence and mortality have steadily worsened over the last decades.1 Surgical excision is the only effective treatment in the localized form of the disease; however, 20-50% of patients experience relapse after radical surgery. Since chemotherapeutic agents are ineffective, several other therapeutic strategies are being evaluated for the treatment of advanced stages of the disease.2 A number of immunotherapeutic approaches have been developed based on the observation that renal cell carcinoma (RCC) can induce an antitumor response by activating immune cells. Indeed, in vitro expansion of T-cell lymphocytes infiltrating RCC lesions yields T-cell responders that exhibit HLA-restricted antitumor activity.3,4 Immunotherapy with IL-2 and interferon (INF)-a achieves a response in 10-20% of cancers, with durable tumor regression occurring only in a limited subset of patients. 5 Furthermore, allogenic stem cell transplantation after nonmyeloablative chemotherapy has recently been evaluated and has been suggested to obtain complete and partial responses ...

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“…IAP proteins can be transiently detected in preimplantation embryos (17,18), although DNA methylation of IAP elements is largely maintained throughout embryogenesis (19,20). In established lines of mouse embryonic stem cells (ESCs) derived from the inner cell mass, IAP elements are already heavily methylated with little detectable IAP expression (21).…”

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confidence: 99%

Repression of Retrotransposal Elements in Mouse Embryonic Stem Cells Is Primarily Mediated by a DNA Methylation-independent Mechanism

Hutnick

Huang²,

Loo³

et al. 2010

Journal of Biological Chemistry

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In defense of deleterious retrotransposition of intracisternal A particle (IAP) elements, IAP loci are heavily methylated and silenced in mouse somatic cells. To determine whether IAP is also repressed in pluripotent stem cells by DNA methylation, we examined IAP expression in demethylated mouse embryonic stem cells (mESCs) and epiblast-derived stem cells. DNA methylation, an epigenetic modification where a methyl group is covalently added to the cytosine of CpG dinucleotides, is catalyzed by a family of DNA methyltransferases (Dnmts) 2 that include de novo (Dnmt3a and -3b) and maintenance methyltransferases (Dnmt1) (1, 2). DNA methylation is known to regulate developmental gene expression, genomic imprinting, X-inactivation, and genomic stability (3-6). Many retrotransposable repetitive elements are heavily methylated, and current evidence supports a causal relationship between DNA methylation and repression of retrotransposons (7-9). Intracisternal A particles (IAPs) are murine endogenous retroviral repetitive elements, with an estimation of over 1000 copies across the haploid murine genome (10 -12). Germ line mutations due to IAP retrotransposition most often occur at intronic sites, disrupting gene expression through premature termination, aberrant splicing, or viral LTR-driven transcription (13). Furthermore, insertional mutagenesis of IAP elements is noted in various murine cancer cell lines with subsequent activation of oncogenes or cytokine genes (14, 15).When expressed, IAP proteins are non-infectious viral particles that are retained in the cisternae of the endoplasmic reticulum (16). IAP proteins can be transiently detected in preimplantation embryos (17, 18), although DNA methylation of IAP elements is largely maintained throughout embryogenesis (19,20). In established lines of mouse embryonic stem cells (ESCs) derived from the inner cell mass, IAP elements are already heavily methylated with little detectable IAP expression (21).Here, we examine expression of IAP proteins in control and demethylated somatic cells, EpiSCs, and mESCs. Using a previously generated antibody against IAP protein (p73) (22) as well as our polyclonal antibody raised against recombinant IAP gag protein (9, 23), we mapped changes in IAP protein levels after Dnmt1 gene deletion in floxed (Dnmt1 2lox/2lox ) mouse embryonic fibroblasts (MEFs) using virus-mediated cre recombinase. Unexpectedly, we found that IAP mRNA and protein levels are not detected in Oct4 Dnmt1Ϫ/Ϫ ESCs but are dramatically increased in demethylated mESC cultures upon in vitro differentiation, suggestive of the presence of DNA methylation-independent repres-

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The expression of intracisternal A particle genes in the preimplantation mouse embryo

Cited by 47 publications

References 58 publications

Gene expression during preimplantation mouse development.

Gene expression during preimplantation mouse development.

Reverse transcriptase inhibitors induce cell differentiation and enhance the immunogenic phenotype in human renal clear‐cell carcinoma

Repression of Retrotransposal Elements in Mouse Embryonic Stem Cells Is Primarily Mediated by a DNA Methylation-independent Mechanism

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