Transcription Factors in the Nervous System: Development, Brain Function, and Diseases

by Editor: Gerald Thiel (University of Saarland Medical Center, Germany)

• ISBN13: 9783527312856
• ISBN10: 3527312854
• Format: Hardcover
• Copyright: 2006-03-01
• Publisher: Blackwell Pub

Summary

This first book to cover neural development, neuronal survival and function on the genetic level outlines promising approaches for novel therapeutic strategies in fighting neurodegenerative disorders, such as Alzheimer's disease. Focusing on transcription factors, the text is clearly divided into three sections devoted to transcriptional control of neural development, brain function and transcriptional dysregulation induced neurological diseases. With a chapter written by Nobel laureate Eric Kandel, this is essential reading for neurobiologists, geneticists, biochemists, cell biologists, neurochemists and molecular biologists.

Author Biography

Since 1997 Gerald Thiel has been professor for Medical Biochemistry and Molecular Biology at the University of the Saarland, Germany. In 1987 he started his career as a post-doc at The Rockefeller University, New York, in the lab of the 2000 Nobel Prize Laureate Paul Greengard. At the same time he was visiting fellow at the Howard Hughes Medical Institute, University of Texas. In 1991 and 1992 he worked as an assistant professor for Molecular and Cellular Neuroscience at The Rockefeller University, and from 1992 to 1997 he was head of lab at the Institute for Genetics, University of Cologne, Germany. His current research interests are the regulation of neuronal gene transcription, signal transduction in the nervous system and the regulation of proliferation and programmed cell death in the nervous system.

Table of Contents

Preface	XVII
List of Contributors	XXI
Color Plates	XXV
Part I Transcription Factors in Neural Development
1 Roles of Hes bH LH Factors in Neural Development
Ryoichiro Kageyarna Jun Hatakeyama, and Toshiyuki Ohtsuka
Abstract	3	(1)
1.1 Introduction	3	(1)
1.2 Structure and Transcriptional Activities of Hes Factors	4	(4)
1.3 Regulation of Hes Gene Expression	8	(1)
1.4 Expression of Hes Genes in the Developing Nervous System	9	(2)
1.5 Maintenance of Neural Stem Cells by Hes Genes	11	(4)
1.6 Promotion of Gliogenesis by Hes Genes	15	(1)
1.7 Maintenance of the Isthmic Organizer by Hes Genes	16	(1)
1.7 Perspective	16	(2)
Acknowledgments	18	(1)
Abbreviations	18	(5)
2 The Role of Pax6 in the Nervous System during Development and in Adulthood: Master Control Regulator or Modular Function?
Nicole Haubst, Jack Favor, and Magdalena Götz
Abstract	23	(1)
2.1 Introduction	23	(3)
2.2 Molecular Features of Pax6	26	(3)
2.2.1 The Paired Domain	26	(1)
2.2.2 The Paired-Type Homeodomain	26	(1)
2.2.3 Different Pax6 Isoforms	27	(1)
2.2.4 Protein-Protein Interactions	28	(1)
2.2.5 Post-Translational Modifications of Pax6	28	(1)
2.3 Function of Pax6 in Development	29	(9)
2.3.1 Function of Pax6 in the Developing Eye	29	(2)
2.3.2 Function of Pax6 in the Developing Brain	31	(1)
2.3.2.1 Telencephalon	33	(1)
2.3.2.2 Diencephalon	36	(1)
2.3.2.3 Cerebellum	37	(1)
2.3.2.4 Spinal Cord	37	(1)
2.4 Function of Pax6 in the Adult Brain	38	(1)
2.5 Mechanisms of Pax6 Function	39	(1)
2.6 Conclusions and Outlook	40	(1)
Abbreviations	41	(12)
3 Phox2a and Phox2b: Essential Transcription Factors for Neuron Specification and Differentiation
Uwe Ernsberger and Hermann Rohrer
Abstract	53	(1)
3.1 Introduction	53	(1)
3.2 Molecular Characteristics of Phox2 Genes and Proteins	54	(2)
3.2.1 Sequence and Gene Structure Conservation in the Animal Kingdom	54	(1)
3.2.2 Transcriptional Activation by Phox2 Proteins	54	(2)
3.3 Physiological Relevance of Phox2 Transcription Factors	56	(4)
3.3.1 Expression Pattern	57	(1)
3.3.2 Effects of Phox2 Gene Mutations	58	(1)
3.3.2.1 Autonomic Neural Crest Derivatives and Visceral Sensory Ganglia	58	(1)
3.3.2.2 Central Noradrenergic Neurons	58	(1)
3.3.2.3 Autonomic Centers in the Hindbrain	59	(1)
3.3.3 Human Mutations	59	(1)
3.4 Molecular Mechanism of Action in Different Lineages	60	(6)
3.4.1 Sympathetic Neurons	60	(1)
3.4.2 Parasympathetic Neurons	61	(1)
3.4.3 Enteric Neurons	62	(1)
3.4.4 Visceral Sensory Neurons of the Geniculate, Petrosal and Nodose Ganglia	62	(1)
3.4.5 Central Noradrenergic Neurons	63	(1)
3.4.6 Autonomic Centers in the Hindbrain	64	(1)
3.4.6.1 Afferent Visceral Centers	64	(1)
3.4.6.2 Efferent Visceral Centers	64	(1)
3.4.7 Oculomotor (nIII) and Trochlear (nIV) Centers	65	(1)
3.5 Conclusions and Outlook	66	(2)
3.5.1 Distinct or Identical Functions for Phox2a and Phox2b?	66	(1)
3.5.2 Master Control Genes for Noradrenergic Differentiation	67	(1)
3.5.3 Master Control Genes for Autonomic Reflex Circuit Generation	68	(1)
Acknowledgments	68	(1)
Abbreviations	69	(6)
4 Functions of LIM-Homeodomain Proteins in the Development of the Nervous System
Yangu Zhao, Nasir Malik, and Heiner Westphal
Abstract	75	(1)
4.1 Introduction	75	(1)
4.2 Common Structural Features and Classification of LIM-HD Proteins	75	(1)
4.3 LIM-HD Proteins and the Development of Invertebrate Nervous Systems	76	(3)
4.3.1 C. elegans	77	(1)
4.3.2 Drosophila	78	(1)
4.4 Functions of LIM-HD Proteins in the Development of Vertebrate Nervous Systems	79	(6)
4.4.1 The Vertebrate Spinal Cord	80	(2)
4.4.2 The Vertebrate Brain	82	(1)
4.4.3 The Olfactory and Visual Sensory Systems	83	(1)
4.4.4 LIM-HD Genes and Early Patterning Events in the Developing CNS	83	(2)
4.5 Factors that Interact with LIM-HD Proteins	85	(2)
4.6 Downstream Targets of LIM-HD Proteins	87	(1)
4.7 Conclusion and Future Directions	88	(1)
Abbreviations	88	(7)
5 The Roles of Serum Response Factor in Brain Development and Function
Bernd Knöll and Alfred Nordheim
Abstract	95	(1)
5.1 Serum Response Factor as a Transcription Factor	95	(1)
5.2 Neuronal Expression Patterns of SRF and Partner Proteins	96	(2)
5.3 SRF Target Genes with Brain Functions	98	(1)
5.4 Essential Requirement for SRF in Neuronal Migration	98	(2)
5.5 SRF and Partner Proteins in Neurite Outgrowth and Axonal Guidance	100	(3)
5.6 SRF-Mediated Gene Expression in Learning and Memory	103	(2)
5.7 SRF in Neurological Disorders	105	(1)
5.8 Perspectives	106	(1)
Acknowledgments	106	(1)
Abbreviations	107	(6)
6 RE-1 Silencing Transcription Factor (REST): Regulation of Neuronal Gene Expression via Modification of the Chromatin Structure
Gerald Thiel and Mathias Hohl
Abstract	113	(1)
6.1 Tissue-Specific Gene Expression: The Molecular Basis for the Function of a Multicellular Organism	113	(1)
6.2 Modular Structure of REST	114	(1)
6.3 Biological Activity of REST	114	(3)
6.4 Mechanism of Transcriptional Repression by REST: Modulation of the Chromatin Structure	117	(3)
6.5 Lessons from the REST Knockout Mouse	120	(2)
6.6 Cell Type-Specific Regulation of REST Target Genes	122	(1)
6.7 The Role of REST in the Differentiation of Neural Stem Cells	123	(1)
6.8 Involvement of REST in Brain Dysfunction and Disease	124	(1)
6.9 Conclusion and Prospects	124	(1)
Acknowledgments	125	(1)
Abbreviations	125	(4)
7 Roles of Tlx1 and Tlx3 and Neuronal Activity in Controlling Glutamatergic over GABAergic Cell Fates
Qiufu Ma and Le-ping Cheng
Abstract	129	(1)
7.1 Introduction	129	(1)
7.2 The Dorsal Horn of the Spinal Cord	130	(1)
7.3 Neurogenesis in the Dorsal Spinal Cord	131	(1)
7.4 The Tlx Family of Homeobox Proteins	131	(3)
7.5 Tlx Gene Expression Marks Sensory Circuits	134	(1)
7.6 Tlx Genes Serve as Binary Switches between Glutamatergic and GABAergic Transmitter Phenotypes	134	(2)
7.7 Binary Decision between GABAergic and Glutamatergic Cell Fates is a Common Theme	136	(1)
7.8 Coupling of Generic Transmitter Phenotypes and Region-Specific Neuronal Identities	136	(1)
7.9 The Plasticity of Neurotransmitter Phenotypes	137	(1)
7.10 Summary and Unsolved Problems	138	(1)
Abbreviations	139	(4)
8 Transcriptional Control of the Development of Central Serotonergic Neurons
Zhou-Feng Chen and Yu-Qiang Ding
Abstract	143	(1)
8.1 Introduction	143	(3)
8.2 Transcription Factors in the Development of 5–HT Neurons	146	(1)
8.3 Transcription Factors Expressed in 5–HT Progenitor Cells	146	(3)
8.3.1 Nkx2.2	146	(2)
8.3.2 Mashl	148	(1)
8.4 Transcription Factors Expressed in the Ventricular Zone and Postmitotic 5–HT Neurons	149	(1)
8.4.1 Gata2 and Gata3	149	(1)
8.5 Transcription Factors Expressed in Postmitotic 5–HT Neurons	150	(5)
8.5.1 Lmx1b	150	(3)
8.5.2 Pet1	153	(2)
8.6 The Relationship between Lmxlb and Pet1	155	(1)
8.7 Conclusions	156	(1)
Abbreviations	156	(7)
9 Role of Mac Homeodomain Factors in the Specification and Differentiation of Motor Neurons and Oligodendrocytes
Jun Cai and Mengsheng Qiu
Abstract	163	(1)
9.1 Introduction	163	(1)
9.2 Structural Features of Nkx Homeobox Genes Involved in Ventral Neural Patterning	164	(2)
9.3 Selective Expression of Nkx Homeobox Genes in the Ventral Neural Tube	166	(2)
9.4 Nkx Genes are Class II Components of the Homeodomain Protein Code for Ventral Neural Patterning and Cell Fate Specification	168	(2)
9.5 Nkx Genes Control the Fate Specification and Differentiation of Motor Neurons	170	(2)
9.5.1 Nkx6.1 and Nkx6.2 have Redundant Activities in Promoting Somatic Motor Neuron Fate Specification	170	(1)
9.5.2 Nkx2.2 Represses Somatic Motor Neuron Fate but Promotes Visceral Motor Neuron Fate	171	(1)
9.5.3 Nkx6 Proteins Control the Migration and Axonal Projection of Hindbrain vMN	172	(1)
9.6 The Role of Nkx Genes in Oligodendrocyte Development	172	(3)
9.6.1 Nkx6 Proteins Promote Olig2 Expression and Ventral Oligodendrogenesis in the Spinal Cord	173	(1)
9.6.2 Nkx6 Proteins Suppress Olig2 Expression and Ventral Oligodendrogenesis in the Rostral Hindbrain	173	(1)
9.6.3 Nkx2.2 Controls the Terminal Differentiation of Oligodendrocytes	174	(1)
9.6.4 Nkx6.2 Homeobox Gene Regulates the Oligodendrocyte Myelination Process	175	(1)
Acknowledgments	175	(2)
Abbreviations	177	(4)
10 Sox Transcription Factors in Neural Development
Michael Wegner and C. Claus Stolt
Abstract	181	(1)
10.1 The Sox Family of Transcription Factors	181	(1)
10.2 Sox Proteins and Neural Competence	182	(1)
10.3 Sox Proteins and the Neuroepithelial Stem Cell	183	(2)
10.4 Sox Proteins and the Neural Crest Stem Cell	185	(4)
10.5 Sox Proteins in Neural Determination and Lineage Decisions	189	(1)
10.6 Sox Proteins in Glial Differentiation	190	(1)
10.7 Sox Proteins in Neuronal Differentiation	191	(2)
10.8 Sox Proteins and their Molecular Mode of Action	193	(2)
10.9 Conservation of Sox Protein Function in Nervous System Development	195	(2)
Acknowledgments	197	(1)
Abbreviations	197	(10)
Part II Transcription Factors in Brain Function
11 The Role of CREB and CBP in Brain Function
Angel Barco and Eric R. Kandel
Abstract	207	(1)
11.1 Introduction	207	(1)
11.2 The CREB Family of Transcription Factors	208	(3)
11.2.1 CREB Family Members and Close Friends	208	(1)
11.2.2 Structural Features of the CREB Family of Transcription Factors	209	(2)
11.2.3 Gene Structure and the Regulation of Expression of CREB Family Members	211	(1)
11.3 The CREB Binding Protein	211	(1)
11.3.1 Structure and Multifunction	212	(1)
11.4 The CREB Activation Pathway	212	(8)
11.4.1 Post-Translational Regulation of CREB Activity	214	(1)
11.4.2 Regulation of CBP Function	214	(2)
11.4.3 Other Modulators of the CREB Pathway	216	(1)
11.4.4 CRE-Binding Activity and CREB Downstream Genes	216	(4)
11.5 Functions of the CREB Activation Pathway in the Nervous System	220	(12)
11.5.1 Regulation of Cellular Responses by the CREB Pathway	220	(1)
11.5.1.1 CREB is Important for Neuronal Survival and Neuroprotection	221	(1)
11.5.1.2 CREB is Required for Axonal Outgrowth and Regeneration	223	(1)
11.5.1.3 CREB has a Role in Neurogenesis and Neuronal Differentiation	223	(1)
11.5.1.5 CB P, Epigenetics and Long-Term Changes in Neuronal Function	228	(1)
11.5.2 Regulation of Systemic Responses by the CREB Pathway	229	(1)
11.5.2.1 CREB and Memory	229	(1)
11.5.2.2 CREB and Circadian Rhythms	231	(1)
11.5.2.3 CREB Function and Development	232	(1)
11.6 Dysregulation of CREB Function and Disease in the Nervous System	232	(4)
11.6.1 CREB and Addiction	233	(1)
11.6.2 Mental Retardation	233	(1)
11.6.3 CREB and Age-Related Memory Impairment	234	(1)
11.6.4 CREB and Neurodegenerative Diseases	234	(1)
11.6.4.1 Huntington Disease	234	(1)
11.6.4.2 Alzheimer's Disease	235	(1)
11.6.5 CREB and Mental Disorders: Depression and other Disorders of Mood	236	(1)
11.7 Conclusions	236	(1)
Abbreviations	236	(7)
12 CCAAT Enhancer Binding Proteins in the Nervous System: Their Role in Development, Differentiation, Long-Term Synaptic Plasticity, and Memory
Cristina M. Alberini
Abstract	243	(1)
12.1 The CCAAT Enhancer Binding Proteins (C/EBPs)	243	(3)
12.2 The Role of C/EBPs in Development and Differentiation	246	(4)
12.2.1 C/EBPs Play a Critical Role in Neurogenesis	247	(1)
12.2.2 C/EBPs Play a Critical Role in Neuronal Cell Death	248	(1)
12.2.3 C/EBP Expression in Glia	249	(1)
12.3 The Role of C/EBPs in Synaptic Plasticity and Memory	250	(5)
Abbreviations	255	(4)
13 The Role of c-Jun in Brain Function
Gennadij Raivich and Axel Behrens
Abstract	259	(1)
13.1 Introduction	259	(1)
13.2 C-Jun Phosphorylation and Upstream Signaling	260	(3)
13.2.1 Mitogen-Activated/Stress-Activated Protein Kinase (MAPK/SAPK) Level	260	(1)
13.2.2 MAP Kinase Kinase (MEK/MKK) and MAP Kinase Kinase Kinase (MEKK) Level	261	(1)
13.2.3 Scaffolding Proteins	261	(1)
13.2.3.1 Multimodal Effects of Deletion	262	(1)
13.3 Development	263	(2)
13.4 Novelty, Learning and Memory, and Addiction	265	(2)
13.4.1 Novelty and Pain	265	(1)
13.4.2 Learning	266	(1)
13.4.3 Addiction	266	(1)
13.5 Seizures and Excitotoxicity	267	(1)
13.6 Ischemia, Stroke, and Brain Trauma	268	(2)
13.6.1 Biochemical Regulation	268	(1)
13.6.2 Role of Jun	268	(1)
13.6.3 Functional Role of JNK Cascade	269	(1)
13.6.4 Direct Evidence	270	(1)
13.7 Axotomy	270	(3)
13.7.1 Regulation	271	(1)
13.7.2 Functional Role: Only Partial Overlap with Jun and JNK	272	(1)
13.8 Conclusions	273	(1)
Abbreviations	273	(12)
14 Expression, Function, and Regulation of Transcription Factor MEF2 in Neurons
Zixu Mao and Xuernin Wang
Abstract	285	(1)
14.1 Introduction	285	(1)
14.2 The MEF2 Family of Transcription Factors	285	(4)
14.2.1 MEF2 Genes and Transcripts	286	(1)
14.2.2 Structure of MEF2 Proteins	286	(2)
14.2.3 Specific Interaction Between MEF2 and DNA	288	(1)
14.3 Expression of Mef2 in Neurons	289	(2)
14.3.1 Expression of mef2 Transcripts in the Central Nervous System	289	(1)
14.3.2 Expression of MEF2 Proteins in Neurons	289	(2)
14.4 Function of Mef2 in Neurons	291	(3)
14.4.1 The Role of MEF2 in Neuronal Differentiation	291	(1)
14.4.2 The Role of MEF2 in Neuronal Survival	291	(2)
14.4.3 Regulatory Targets of MEF2 in Neurons	293	(1)
14.5 Regulation of MEF2 in Neurons	294	(7)
14.5.1 Regulation of MEF2 Transactivation Potential	294	(2)
14.5.2 Regulation of MEF2 DNA Binding	296	(1)
14.5.3 Regulation of MEF2 Stability	297	(1)
14.5.4 Regulation of MEF2 Subcellular Localization	298	(1)
14.5.5 Regulation of MEF2 by Alternative Splicing	299	(1)
14.5.6 Regulation of MEF2 by Interaction with Co-Regulators	299	(1)
14.5.7 Regulation of MEF2 by Calcium Signaling	300	(1)
14.6 Future Studies	301	(1)
Acknowledgments	301	(1)
Abbreviations	302	(5)
15 RORa: An Orphan that Staggers the Mind
Peter M. Gent and Bruce A. Hamilton
Abstract	307	(1)
15.1 Introduction	307	(1)
15.2 Identification and Biochemical Properties of RORa	308	(5)
15.2.1 Identification	308	(1)
15.2.2 Isoforms	308	(1)
15.2.3 RORa Binding and Response Elements	308	(2)
15.2.4 Crosstalk Between Factors	310	(1)
15.2.5 Ligands or Cofactors?	310	(1)
15.2.6 Co-activators	311	(1)
15.2.7 Co-repressors	311	(1)
15.2.8 Activation and Regulation of RORa Expression	312	(1)
15.2.9 RORa Expression in the Nervous System	313	(1)
15.3 Role of RORa in the Developing Cerebellum	313	(3)
15.4 Roles of RORa in Other Tissues	316	(1)
15.4.1 Suprachiasmatic Nuclei	316	(1)
15.4.2 Peripheral Tissues	317	(1)
15.5 In-Vivo Identification of RORa Targets	317	(4)
15.5.1 Genetic Program Controlled by RORa in the Cerebellum	317	(1)
15.5.2 Direct or Indirect Targets?	318	(1)
15.5.3 Developmental Signaling Genes	318	(2)
15.5.4 Calcium Signaling and Synaptic Function Genes	320	(1)
15.6 Implication of RORa in SCA1 Disorder	321	(1)
15.7 Summary	321	(1)
Abbreviations	322	(5)
16 The Role of NF-kB in Brain Function
Barbara Kaltschmidt, Ilja Mikenberg, Darius Widera, and Christian Kaltschmidt
Abstract	327	(1)
16.1 Introduction	327	(1)
16.2 The NF-kB/Rel Family of Transcription Factors	327	(3)
16.2.1 The IkB Proteins: Inhibitors of NF-kB	328	(2)
16.3 Canonical NF-kB Activation	330	(13)
16.3.1 Activators of NF-kB	335	(2)
16.3.2 Repressors of NF-kB	337	(1)
16.3.3 Synaptic NF-kB	338	(5)
Acknowledgments	343	(1)
Abbreviations	343	(10)
17 Calcineurin/NFAT Signaling in Development and Function of the Nervous System
Isabella A. Graef, Gerald R. Crabtree, and Fan Wang
Abstract	353	(1)
17.1 Biochemistry of NEAT Signaling	353	(8)
17.1.1 Biochemical Basis of Coincidence Detection and Signal Integration by NFAT Transcription Complexes	353	(1)
17.1.2 The Mechanism of Nuclear Entry of NFATc Proteins.	354	(2)
17.1.3 Discrimination of Calcium Signals and the Nuclear Exit of NFATc Proteins	356	(3)
17.1.4 Combinatorial Assembly of NFAT Transcription Complexes Determines Specificity of Ca²+ Responses	359	(1)
17.1.5 Dedication of CaN to NFATc Family Members	360	(1)
17.1.6 Evolution of the Genes that Encode the Cytosolic Components, the NFATc Family	360	(1)
17.2 Roles of NFAT Signaling in Axonal Outgrowth and Synaptogenesis	361	(1)
17.3 A Possible Role for NFAT Signaling in Defining Pathways for Both Vessels and Peripheral Nerves	362	(4)
17.4 Roles of NFAT Signaling in Later Development: Responses to Spontaneous Activity	366	(4)
17.5 The Role of NFAT in Neuronal Survival	370	(1)
17.6 Small Molecule Inhibitors of CaN are Powerful Probes of Neuronal Development	371	(2)
17.6.1 The Mechanism of Action of FK506 and Cyclosporine A	371	(1)
17.6.2 Use of CsA and FK506 in Studies of Neural Development and Function	372	(1)
17.6.3 Assessing CaN Activity	372	(1)
17.7 NFAT Signaling and Transcriptional Control in Human Disease	373	(1)
17.7.1 Possible Defects in NFAT Signaling in Human Schizophrenia	373	(1)
17.7.2 Down Syndrome and NFAT Signaling	373	(1)
17.8 Conclusion	374	(1)
Abbreviations	374	(5)
18 Stimulus-Transcription Coupling in the Nervous System: The Zinc Finger Protein Egr-1
Oliver G. Rössler, Luisa Stefano, Inge Bauer, and Gerald Thiel
Abstract	379	(1)
18.1 Introduction	379	(1)
18.2 Modular Structure of Egr-1	379	(2)
18.3 Intracellular Signaling Cascades Converging at the Egr-1 Gene	381	(2)
18.4 The Egr-1 Promoter	383	(2)
18.5 Lessons from Egr–/–Deficient Mice	385	(1)
18.6 Egr-1 Regulates Synaptic Plasticity in the Nervous System	386	(1)
18.7 Correlation Between Proliferation of Astrocytes and Egr-1 Biosynthesis	387	(1)
18.8 Egr-1: A "Pro-apoptotic Protein" for Neurons?	387	(3)
18.9 Conclusions and Future Prospects	390	(1)
Acknowledgments	391	(1)
Abbreviations	391	(8)
Part III Transcription Factors in Neuronal Diseases
19 The Presenilin/g-Secretase Complex Regulates Production of Transcriptional Factors: Effects of FAD Mutations
Nikolaos K. Robakis and Philippe Marambaud
Abstract	399	(1)
19.1 Introduction	399	(1)
19.2 Processing of APP and FAD	400	(2)
19.3 The Presenilins	402	(1)
19.4 The Notch1 ICD (NICD) Mediates Transcriptional and Developmental Functions Associated with Notchl Receptor	403	(1)
19.5 Transcriptional Function of the APP ICD (AICD)	404	(1)
19.6 PS1 and b-Catenin-Mediated Transcription	405	(1)
19.7 PS1 is a Critical Regulator of Cadherin-Dependent Cell-Cell Adhesion and Signal Transduction	406	(2)
19.8 Conclusions	408	(1)
Abbreviations	408	(9)
20 Transcriptional Abnormalities in Huntington's Disease
Dimitri Krainc
Abstract	417	(1)
20.1 Introduction	417	(1)
20.2 Mutant Huntingtin Interferes with Specific Components of General Transcriptional Machinery	418	(4)
20.3 Mutant Huntingtin Disrupts Sp1—TAF4 Transcriptional Pathway	422	(2)
20.4 Deregulation of CRE-Dependent Transcription in HD	424	(11)
20.5 Summary	435	(1)
Abbreviations	435	(1)
Acknowledgments	436	(5)
Index	441