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A Direct Repeat Sequence at theRasgrf1Locus and Imprinted Expression
Institution:1. Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, 14263-0001;2. Division of Human Cancer Genetics, Ohio State University, 420 West 12th Avenue, Columbus, Ohio, 43210;3. Department of Biochemistry and Department of Pediatrics, State University of New York at Buffalo, 3435 Main Street, Buffalo, New York, 14214;4. Genome Science Laboratory, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba City, Ibaraki, 305, Japan;1. School of Life Sciences, Liaoning University, Shenyang 110036, China;2. Institute of Animal Husbandry and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110036, China;3. Centre for Ecology and Conservation, School of Biosciences, University of Exeter, Cornwall Campus, Penryn TR12 9EZ, UK;1. School of Optometry and Vision Science, Queensland University of Technology, Brisbane, Queensland, Australia;2. Department of Psychology, Clemson University, SC, USA;1. Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC, Brazil;2. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário – Trindade, 88040-900 Florianópolis SC, Brazil;1. College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, 88 East Wenhua Road, Jinan 250014, PR China;2. Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, 202 Gongye North Road, Jinan 250100, PR China;3. School of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China;1. COMUE Université Bretagne Loire, Oniris, Nantes-Atlantic College of Veterinary Medicine and Food Sciences, Nantes, France;2. Department of Animal Biology, School of Integrative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.;3. Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.;4. Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.;5. Program in Ecology, Evolution and Conservation, University of Illinois at Urbana-Champaign, Urbana, IL, U.S.A.
Abstract:Genomic imprinting is an epigenetic modification that can lead to parental-specific monoallelic expression of specific autosomal genes. While methylation of CpG dinucleotides is thought to be a strong candidate for this epigenetic modification, little is known about the establishment or maintenance of parental origin-specific methylation patterns. We have recently identified a portion of mouse chromosome 9 containing a paternally methylated region associated with a paternally expressed imprinted gene, Ras protein-specific guanine nucleotide-releasing factor 1 (Rasgrf1). This area of chromosome 9 also contains a short, direct tandem repeat in close proximity to a paternally methylatedNotI site 30 kb upstream ofRasgrf1.Short, direct tandem repeats have been found associated with other imprinted genes and may act as important regulatory structures. Here we demonstrate that two rodent species (MusandRattus) contain a similar direct repeat structure associated with a region of paternal-specific methylation. In both species, theRasgrf1gene shows paternal-specific monoallelic expression in neonatal brain. A more divergent rodent species (Peromyscus) appears to lack a similar repeat structure based on Southern Blot analysis.Peromyscusanimals show biallelic expression ofRasgrf1in neonatal brain. These results suggest that direct repeat elements may play an important role in the imprinting process.
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