Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently detected de-novo transcripts of the predominantly muscle-specific myotonin protein kinase gene in human preimplantation embryos from the 1-cell to the 4-cell stages. Others have shown de-novo transcripts of the Y-linked genes, ZFY and SRY, in the 1-cell zygote. In order to assess the significance of early transcription of these predominantly tissue-specific genes in preimplantation development, we have analysed individual human oocytes and preimplantation embryos for the presence of transcripts of two further tissue-specific genes, alpha-globin and beta-globin, and two house-keeping genes, HPRT and APRT. Reverse transcriptase polymerase chain reaction assays were developed to the required single cell sensitivity, using human red blood cells and fibroblasts, prior to their application to human oocytes and embryos. As expected, transcripts of the house-keeping genes, HPRT and APRT, were detected at all stages of preimplantation development. Transcripts of 'tissue-specific' alpha-globin were readily detected in preimplantation embryos from the 1-cell stage. However, transcripts of beta-globin were detected only rarely (in only one of the 11 embryos analysed). This difference may be due to the fact that alpha-globin contains a CpG island. A survey of the data on gene expression in early human development suggests that CpG-island-containing genes may be expressed in preimplantation embryos. Expression of these genes in gametes and early embryos may be involved in the survival of CpG islands in evolution.
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PMID:Transcription of tissue-specific genes in human preimplantation embryos. 940 90

DNA in somatic tissue is characterized by a bimodal pattern of methylation, which is established in the animal through a series of developmental events. In the mouse blastula, most DNA is unmethylated, but after implantation a wave of de novo methylation modifies most of the genome, excluding the majority of CpG islands, which are mainly associated with housekeeping genes. This genomic methylation pattern is broadly maintained during the life of the organism by maintenance methylation, and generally correlates with gene expression. Experiments both in vitro and in vivo indicate that methylation inhibits transcription. It has not yet been possible, however, to determine the role of DNA methylation on specific sequences during normal development. Cis-acting regulatory elements and trans-acting factors appear to be involved in both stage- and tissue-specific demethylation processes. Sp1-like elements have a key role in protecting the CpG island of Aprt (encoding adenine phosphoribosyltransferase) from de novo methylation, and when these elements are specifically mutated, the Aprt CpG island becomes methylated in transgenic mice. We have now characterized an embryo-specific element from the CpG island sequence upstream of Aprt that can protect itself from de novo methylation in transgenic mice as well as reduce methylation of flanking sequences. We placed this element on a removable cassette adjacent to a human HBB (encoding beta-globin) reporter and generated a transgene whose methylation pattern can be switched in vivo. Analysis of globin transcription in this system showed that methylation in cis inhibits gene expression in a variety of tissues, indicating that DNA modification may serve as a global genomic repressor.
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PMID:DNA methylation represses transcription in vivo. 1036 68

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm beta-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state.
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PMID:VEZF1 elements mediate protection from DNA methylation. 2006 23