Genomic Imprinting

ISBN-13: 9780387775753 / Angielski / Twarda / 2008 / 126 str.

Opis

Genomic imprinting refers to a recently discovered phenomenon in which the expression pattern of an allele depends on whether that allele was inherited from the mother or the father. This difference in expression strategy correlates with differences in the epigenetic state of the two alleles. These epigenetic differences include DNA methylation at CpG dinucleotides, as well as modifications on the histones associated with the locus. In the simplest possible cases, the promoter region of the imprinted gene is methylated during oogenesis, but not spermatogenesis (or vice versa). This methylation (and its accompanying histone modifications) results in inactivation of the modified allele. Of course, most imprinted genes do not fall into this simplest case. The goal of this book is neither to provide a basic introduction to imprinting, nor to provide a comprehensive survey of the current state of the field (which would necessarily span multiple books). Rather, the book covers on some of the more recent advances, with the goal of drawing attention to some of the emerging subtleties and complexities associated with imprinted genes.

Spis treści

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