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Genomic Imprinting
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CONTENTS 1. DNA Methylation Reprograming in the Germ Line....... 1 Diane J. Lees-Murdock and Colum P. Walsh Introduction.......................................................................................................................... 1 Methylation of Repeats and Genome Stability................................................................... 3 Demethylation in the Germ Line......................................................................................... 3 De Novo Methylation in the Developing Gametes............................................................. 8 Fate of Methylation Differences Inherited from the Gametes in the Early Embryo.... 10 Methylation Enforces Transcriptional Silencing and Suppresses Recombination....... 11 Repeats Attract Methylation, while Transcription Factors Block It.............................. 12 Conclusions......................................................................................................................... 12 2. Control of Imprinting at the Gnas Cluster........................ 16 Jo Peters and Christine M. Williamson Background........................................................................................................................ 16 Extent of the Region............................................................................................................ 17 Transcripts at the Gnas Locus........................................................................................... 18 Proteins Encoded at the Gnas Complex Locus................................................................. 18 Function of Proteins Encoded at the Gnas Locus............................................................ 18 Imprinting Centers............................................................................................................. 19 The Exon 1A DMR Controls the Expression of Gnas...................................................... 21 The Nespas DMR is the Principal ICR in the Gnas Cluster........................................... 21 Interaction between the Nespas DMR and the Exon 1A DMR....................................... 22 The Role of Nespas.............................................................................................................. 23 The Role of the Exon 1A DMR.......................................................................................... 23 Conclusions......................................................................................................................... 24 3. The GNAS locus and Pseudohypoparat hyroidism............. 27 Murat Bastepe Introduction........................................................................................................................ 27 Inactivating Gsa mutations and multiple hormone resistance: PHP-Ia..................... 29 Role of tissue- and parental origin-specific Gsa expression in hormone resistance............................................................................................... 30 Mutations affecting the imprinting control regions of GNAS and PTH-resistance: PHP-Ib.................................................................................... 32 Conclusion.......................................................................................................................... 36 xvi Contents 4. Imprinted Genes, Postnatal Adaptations and Enduring Effects on Energy Homeostasis ....... 41 Margalida Frontera, Benjamin Dickins, Antonius Plagge and Gavin Kelsey Introduction........................................................................................................................ 41 Imprinted Gene Syndromes and Obesi

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