Chromatin and Gene Regulation Molecular Mechanisms in Epigenetics

by Turner, Bryan M.

• ISBN13: 9780865427433
• ISBN10: 0865427437
• Edition: 1st
• Format: Paperback
• Copyright: 2002-02-01
• Publisher: Wiley-Blackwell

Summary

Written in an informal and accessible style, Chromatin and Gene Regulation enables the reader to understand the science of this rapidly moving field. Chromatin is a fundamental component in the network of controls that regulates gene expression. Many human diseases have been linked to disruption of these control processes by genetic or environmental factors, and unravelling the mechanisms by which they operate is one of the most exciting and rapidly developing areas of modern biology. Chromatin is central both to the rapid changes in gene transcription by which cells respond to changes in their environment and also to the maintenance of gene expression patterns from one cell generation to the next. This book will be an invaluable guide to undergraduate and postgraduate students in the biological sciences and all those with an interest in the medical implications of aberrant gene expression.

Author Biography

Bryan M. Turner is Professor of Experimental Genetics at School of Cancer Sciences, Institute of Biomedical Research, University of Birmingham in Birmingham, UK.
He was educated at University College London, where he earned his BSc in Biochemistry and PhD in Human Biochemical Genetics.

Table of Contents

Preface	xi
Prologue	1	(6)
Controlling Transcription: Shared Aims and Common Mechanisms	7	(18)
Introduction	7	(1)
Some general principles	7	(2)
Transcription in prokaryotes	9	(4)
Genetic switches in bacteria	13	(12)
Transcription in Eukaryotes: The Problems of Complexity	25	(19)
Introduction	25	(1)
The emergence of eukaryotes	25	(4)
The transcription machinery in eukaryotes	29	(5)
General transcription factors, TAFs and the PolII pre-initiation complex	34	(4)
Transcription by Poll and PolIII	38	(1)
The elongation stage	39	(1)
Experimental considerations	40	(1)
Large genome problems: why are things so complicated?	40	(4)
The Nucleosome: Chromatin's Structural Unit	44	(15)
Introduction	44	(1)
Exploring how DNA is packaged in the nucleus	44	(6)
The structure of the nucleosome	50	(9)
Histone Tails: Modifications and Epigenetic Information	59	(16)
Introduction	59	(1)
The histone tails	60	(2)
Histone modifications	62	(10)
Histone variants	72	(3)
Higher-Order Chromatin Structures and Nuclear Organization	75	(26)
Introduction	75	(1)
The 30 nm fibre	75	(5)
DNA loops	80	(3)
The nuclear matrix and chromosome scaffolds	83	(4)
Scaffold/matrix associated regions (SARs and MARs)	87	(2)
Chromosome bands and functional domains	89	(6)
Nuclear domains and structure in the interphase nucleus	95	(6)
Transcription in a Chromatin Environment	101	(25)
Introduction	101	(1)
Genes are packaged into nucleosomes, even when they are being transcribed	102	(5)
Genetic experiments in yeast show the importance of histones for gene regulation	107	(1)
Changes in chromatin structure precede gene activation	108	(2)
Increased histone acetylation can precede or accompany the onset of transcription	110	(3)
DNaseI hypersensitive sites	113	(2)
Nucleosome positioning in vitro and in vivo	115	(6)
Chromatin domains	121	(5)
How the Transcription Machinery Deals with Chromatin	126	(20)
Introduction	126	(1)
In vitro studies of transcription factor binding	126	(5)
A crowded nucleosome: Mouse Mammary Tumour Virus nucleosome B	131	(7)
The opportunities presented by DNA replication	138	(3)
Chromatin and the elongation stage of transcription	141	(5)
Chromatin Remodelling Machines	146	(26)
Introduction	146	(1)
Nucleosome remodelling enzymes	146	(7)
Histone acetyltransferases (HATs)	153	(5)
Histone deacetylases	158	(4)
The nuclear receptors	162	(3)
Chromatin and cancer	165	(7)
Heterochromatin	172	(24)
Introduction	172	(1)
α and β heterochromatin in Drosophila	173	(2)
Facultative and constitutive heterochromatin	175	(1)
Heterochromatin DNA	175	(4)
Heterochromatin genes	179	(1)
Heterochromatin proteins	180	(3)
Position effect variegation	183	(8)
Heterochromatin and gene expression in mammals	191	(5)
Long-Term Silencing of Gene Expression	196	(25)
Introduction	196	(1)
DNA methylation	196	(9)
Silencing at telomeres and mating type loci in yeast	205	(16)
Cellular Memory and Imprinting	221	(28)
Introduction	221	(2)
Maintenance of transcriptional states	223	(13)
Imprinted genes	236	(13)
Mechanisms of Dosage Compensation	249	(26)
Introduction	249	(1)
Methods of sex determination	249	(4)
Dosage compensation in mammals	253	(8)
Dosage compensation in Drosophila	261	(7)
Dosage compensation in C. elegans	268	(3)
Lessons from dosage compensation	271	(4)
Index	275