Umfang:
Online-Ressource (XIII, 465p. 25 illus., 14 illus. in color, digital)
ISBN:
9781461433453
Serie:
SpringerLink
Inhalt:
In multicellular organisms the establishment, maintenance, and programmed alterations of cell-type specific gene expression patterns are regulated by epigenetic mechanisms. Thus, epigenetic alterations (DNA methylation, DNA associated Polycomb-Trithorax protein complexes, histone modifications) ensure the unique transcriptional activity and phenotypic diversity of diploid cells that carry identical or nearly identical DNA sequences.Because DNA methyltransferase I (DNMT1) associates with replication foci during S phase and prefers hemimethylated DNA as a substrate, DNMT1 ensures the clonal propagation of cytosine methylation patterns (maintenance methylation). Thus, DNA methylation may provide a memory function by helping progeny cells to "remember their proper cellular identity. An alternative system of epigenetic memory, the Polycomb and Trithorax groups of protein complexes, that may operate both independently from and in concert with DNA methylation, ensures the heritable regulation of gene expression via modification of histone tails. The complex interplay of epigenetic regulatory mechanisms permits both the dynamic modulation of gene expression and the faithful transmission of gene expression patterns to each progeny cell upon division. These carefully orchestrated processes can go wrong, however, resulting in epigenetic reprogramming of the cells that may manifest in pathological changes, as it was first realized during the studies of epigenetic alterations in malignant tumors. By now it became a well established fact that not only genetic changes, but also the disruption of epigenetic regulation can result in carcinogenesis and tumor progression. Scientists working in other fields soon followed the pioneering work of cancer researchers, and revealed that epigenetic dysregulation forms the basis of a wide spectrum of humandiseases.
Anmerkung:
Description based upon print version of record
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Patho-Epigenetics of Disease; Preface; Contents; Contributors; Chapter 1: The Impact of Foreign DNA Integration on Tumor Biology and Evolution via Epigenetic Alterations; 1.1 Introduction; 1.2 Résumé of Our Previous Work on DNA Methylation; 1.3 Manipulations of the Genome Can Lead to Extensive Alterations of Its Epigenetic Pro file; 1.4 Impact of (Repetitive) Foreign DNA Insertions on Evolution; 1.5 Role in Tumor Disease; 1.6 HIV Infections and AIDS; 1.7 A Caveat Towards Manipulations on Existing Eukaryotic Genomes; 1.8 Future Perspectives; References
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Chapter 2: The Role of DNMT3B Mutations in the Pathogenesis of ICF Syndrome2.1 Introduction; 2.1.1 ICF Syndrome: A Chromatin Disorder of Gene Silencing; 2.1.1.1 Clinical Manifestation and Diagnosis; 2.1.1.2 Genetics: ICF Type 1 and ICF Type 2; 2.1.2 DNMT3B Mutations: How Do They Produce the ICF Phenotype?; 2.1.2.1 Setting and Maintenance of DNA Methylation in Mammals: A Novel View; 2.1.2.2 Dnmt3s Target Speci fi city: Is it a Matter of the Neighbors?; 2.1.2.3 Mouse Models for DNMT De fi ciency; 2.1.2.4 Functional Domains and Enzymatic Properties of DNMT3 Enzymes
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2.1.2.5 Mutations Perturbing DNMT3B Function at Multiple Levels2.1.2.6 Epigenetic Network: Relationship of DNMT3B Perturbation to the ICF Phenotype; 2.2 Conclusions and Perspectives; References; Chapter 3: Dysfunction of the Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome; 3.1 Introduction; 3.2 Clinical Features of RTT; 3.3 RTT Neuropathology; 3.4 Links to Autism Spectrum Disorders; 3.5 Gene Function: MeCP2; 3.6 Model Systems: Mecp2 Knockout, Mecp2 Mutant, and MeCP2 Knock-In Mice; 3.7 Reversal of Behavioral and Cellular Impairments in MeCP2-Based Mouse Models of RTT; 3.8 Summary; References
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Chapter 4: Epigenetic Alterations in Glioblastoma Multiforme4.1 Overview: The Epigenome and CNS Malignancy; 4.2 Glioblastoma Multiforme: Description and Incidence; 4.3 Primary and Secondary GBM: Clinical and Genetic Characteristics; 4.4 Distinct Epigenetic Alterations in Primary Versus sGBM: Early Clues to a Hypermethylation Phenotype; 4.5 IDH Mutation and the DNA Hypermethylator Phenotype; 4.6 Mechanistic Links Between IDH Mutation and DNA Hypermethylation in GBM: The Role of 5-Hydroxymethylcytosine (the Sixth Base); 4.7 DNA Hypomethylation: A Common Feature of the De Novo GBM Genome
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4.8 GBM Therapy Targeting Epigenetic Pathways4.9 Perspective and Future Challenges; References; Chapter 5: Aberrant Epigenetic Regulation in Breast Cancer; 5.1 Introduction; 5.2 Epigenetics; 5.3 Methylation; 5.3.1 Aberrant Methylation Patterns in Cancers; 5.3.2 Breast Cancer Genes Showing Aberrant Methylation; 5.3.2.1 Estrogen Receptor Alpha; 5.3.2.2 Ras-Associated Domain Family Member 1 Gene; 5.3.2.3 Breast Cancer 1; 5.3.3 Genome-Wide Methylation Patterning; 5.4 Chromatin; 5.5 Methods Used to Measure Histone Modifications; 5.5.1 Chromatin Modi fi cation in Breast Cancer
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5.5.1.1 Polycomb Repressor Complex 1 and 2
Weitere Ausg.:
ISBN 9781461433446
Weitere Ausg.:
Buchausg. u.d.T. ISBN 9781461433446
Sprache:
Englisch
DOI:
10.1007/978-1-4614-3345-3
URL:
Volltext
(lizenzpflichtig)
Mehr zum Autor:
Niller, Hans Helmut
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