Taneja bHLH Transcription Factors in Development and Disease

1. Auflage 2014
ISBN: 978-0-12-407154-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 110, 398 Seiten

Reihe: Current Topics in Developmental Biology

This new volume of Current Topics in Developmental Biology provides a comprehensive set of reviews on bHLH transcription factors.ÿ bHLH factors are vastly recognized for their diverse roles in developmental processes and their dysfunction underlies various human pathologies.ÿ Each chapter is authoritatively written by a leading expert in the field and discusses every possible aspect of this huge and diverse field. - Covers the area of basic helix-loop-helix (bHLH) transcription factors in development and disease - International board of authors - Provides a comprehensive set of reviews on our current understanding on the function of bHLH factors in development of various tissues and how de-regulation of these factors can cause, or is linked to, various human diseases

Autoren/Hrsg.

Taneja, Reshma

Inhaltsverzeichnis

1;Front Cover;1
2;bHLH Transcription Factors in Development and Disease;4
3;Copyright;5
4;Contents;6
5;Contributors;10
6;Preface;14
7;Chapter One: Molecular and Cellular Regulation of Skeletal Myogenesis;18
7.1;1. Introduction;19
7.2;2. Molecular Features of the Mrfs;20
7.2.1;2.1. Mrfs at the nodal point of cell identity-similarities and differences;20
7.2.2;2.2. Negative regulation of Mrf potency: establishing the onset of differentiation;22
7.3;3. Skeletal Muscle Development;24
7.3.1;3.1. Giving birth to muscle-some unusual twists;24
7.3.2;3.2. Diversity in origin and modular design;26
7.3.3;3.3. Lessons from gene deletions;30
7.3.4;3.4. Upstream regulators;31
7.3.5;3.5. Temporal specification of myogenesis;36
7.3.6;3.6. Enhancer interplays in regulation of the Mrfs;38
7.3.7;3.7. Lessons from lineage tracing and cell ablation studies-a cautionary tale;39
7.4;4. Mrfs as Transdifferentiation Factors;41
7.4.1;4.1. In vitro studies provide a new view on transdifferentiation;41
7.4.2;4.2. Transdifferentiation in vivo;45
7.4.3;4.3. From transdifferentiation studies to in-dish models of disease;46
7.5;5. Induction of Muscle-Specific Gene Expression;50
7.5.1;5.1. Cooperation between the Mrfs and other transcription factors;50
7.5.2;5.2. Mrfs and chromatin remodeling;51
7.6;6. Genome-Wide Studies and the Paradox of Excess Binding Sites for the Mrfs;54
7.6.1;6.1. Myod binding through the genome: productivity or remodeling?;55
7.6.2;6.2. Private versus shared E-boxes and lineage-determined chromatin accessibility;57
7.6.3;6.3. Lessons learned from Pax3/7 genome-wide studies;59
7.7;7. Molecular Evolution and Conservation in Other Species;62
7.8;8. Conclusions and Perspectives;64
7.9;Acknowledgments;71
7.10;References;71
8;Chapter Two: Proneural bHLH Genes in Development and Disease;92
8.1;1. Introduction to Proneural Genes;93
8.1.1;1.1. Identification and functional characterization of proneural genes in Drosophila;93
8.1.2;1.2. Introduction to vertebrate proneural genes;96
8.2;2. Proneural Functions of the Neurogenin Genes in Development;98
8.2.1;2.1. Neurog1 and Neurog2 identification and functions in the developing PNS;98
8.2.1.1;2.1.1. Neurog1 and Neurog2 specify distinct neuronal phenotypes in dorsal root ganglia;98
8.2.1.2;2.1.2. Neurog1 and Neurog2 function similar to Drosophila proneural genes in the cranial placodes;99
8.2.2;2.2. Neurog1 and Neurog2 function in the developing CNS;100
8.2.2.1;2.2.1. Neurog2 specifies distinct neuronal phenotypes in different regions of the neural tube;100
8.2.2.2;2.2.2. Neurog2 proneural functions are tightly regulated in the developing neocortex via multiple mechanisms;103
8.2.2.3;2.2.3. Neurog1 and Neurog2 have distinct and overlapping functions in the neocortex;105
8.2.3;2.3. Neurog3 identification and function in the developing CNS;106
8.2.4;2.4. Neurog3 function in the developing pancreas;107
8.2.5;2.5. Neurog3 function in the enteroendocrine system;108
8.3;3. Atoh1/Atoh7 Proneural Functions in Development;110
8.3.1;3.1. Introduction to Atoh family proneural genes;110
8.3.2;3.2. Atoh1 function in rhombic lip derivatives;110
8.3.3;3.3. Atoh1 function in inner ear development;111
8.3.4;3.4. Atoh1 function in the intestinal epithelium;111
8.3.5;3.5. Atoh7 function in the retina;112
8.4;4. Ascl1 Proneural Functions in Development;113
8.4.1;4.1. Ascl1 identification and function in the developing PNS;113
8.4.2;4.2. Ascl1 proneural functions in the developing CNS;114
8.4.2.1;4.2.1. Ascl1s ability to specify more than one cell fate is regulated by target gene selection and posttranslational modi...;116
8.4.3;4.3. Ascl1 and neuronal reprogramming;117
8.5;5. Proneural Genes in Human Disease (Table 2.1);118
8.5.1;5.1. Human developmental disorders;118
8.5.2;5.2. Neurologic and neuropsychiatric disease;121
8.5.3;5.3. Proneural genes in cancer;122
8.5.3.1;5.3.1. Atoh1 in nervous system and gastrointestinal cancer;122
8.5.3.2;5.3.2. ASCL1 in nervous system cancers;123
8.5.3.3;5.3.3. ASCL1 in neuroendocrine cancers;124
8.5.4;5.4. Proneural genes in diabetes and enteroendocrine disorders;125
8.6;References;127
9;Chapter Three: The Hand2 Gene Dosage Effect in Developmental Defects and Human Congenital Disorders;146
9.1;1. Introduction;147
9.2;2. Cloning of Hand Genes and Their Expression Patterns;149
9.3;3. Developmental Functions of Hand2;151
9.4;4. Gene Dosage Effect of Hand2 in Mouse Embryogenesis;157
9.5;5. Disruption of Hand2 Dosage Causes Human Diseases;159
9.6;6. Future Perspectives;163
9.7;Acknowledgments;164
9.8;References;164
10;Chapter Four: E Proteins in Lymphocyte Development and Lymphoid Diseases;170
10.1;1. Introduction;171
10.2;2. E Proteins;172
10.2.1;2.1. E proteins and cell-cycle control;174
10.3;3. E Proteins in Lymphocyte Development;174
10.3.1;3.1. Antigen receptor recombination;174
10.3.2;3.2. Lymphocyte selection;176
10.4;4. E Proteins in B Cell Development;177
10.5;5. E Protein Roles in Mature B Cells;181
10.6;6. E Protein Roles in T Cell Development;182
10.7;7. Roles of E Proteins in Mature T Cells;186
10.8;8. E Proteins in Lymphoid Diseases;187
10.8.1;8.1. E proteins in autoimmunity;187
10.8.2;8.2. E proteins in cancer;189
10.8.2.1;8.2.1. Burkitt Lymphoma;189
10.8.2.2;8.2.2. E2A-PBX1 translocation in B cell acute lymphocytic leukemia;192
10.8.2.3;8.2.3. E proteins in T cell cancers;194
10.9;9. Conclusion;195
10.10;Acknowledgments;196
10.11;References;196
11;Chapter Five: Id Proteins: Small Molecules, Mighty Regulators;206
11.1;1. Introduction;207
11.2;2. The Structure and Function of Id Proteins;207
11.3;3. Regulation of Id Gene Expression;209
11.4;4. Id Proteins in Stem Cell Maintenance;210
11.4.1;4.1. Hematopoietic stem cells;211
11.4.2;4.2. Neural stem cells;212
11.5;5. Id Proteins in Vasculogenesis;213
11.6;6. Id Proteins in Cancer;215
11.7;7. Id Proteins in the Immune System;219
11.8;8. Id Proteins in Adipogenesis;223
11.9;9. Concluding Remarks;225
11.10;References;225
12;Chapter Six: E(spl): Genetic, Developmental, and Evolutionary Aspects of a Group of Invertebrate Hes Proteins with Close ...;234
12.1;1. E(spl): From a Spontaneous Dominant Mutation to a Group of Core Developmental Regulators;236
12.2;2. E(spl) Proteins-Where Did They All Come From?;240
12.3;3. Regulation of E(spl) Genes;242
12.4;4. Functions of E(spl) Proteins in Drosophila;248
12.4.1;4.1. Lateral inhibition of neural precursors in the CNS;249
12.4.2;4.2. Lateral inhibition of neural precursors in the PNS-Inhibition of proneural proteins;250
12.4.3;4.3. Lateral inhibition of neuronal precursors in the retina-Autoinhibition of E(spl);254
12.4.4;4.4. E(spl) in other instances of Notch-mediated lateral inhibition;257
12.4.5;4.5. Involvement of E(spl) in other developmental processes-Interplay with the RTK/MAPK pathway;258
12.4.6;4.6. E(spl) in tissue maintenance and regeneration;261
12.4.7;4.7. E(spl) can synergize with other bHLH-O proteins;262
12.5;5. E(spl) Function in Other Species;265
12.6;6. Closing Remarks;267
12.7;Acknowledgments;268
12.8;References;268
13;Chapter Seven: Expression Dynamics and Functions of Hes Factors in Development and Diseases;280
13.1;1. Introduction;281
13.2;2. Hes Family Members and Protein Structures;281
13.3;3. Hes General Functions;283
13.4;4. Roles of Hes Factors in Various Tissues;284
13.5;5. Hes Functions in the Central Nervous System;286
13.5.1;5.1. Hes genes in NS cells;286
13.5.2;5.2. Hes genes in brain morphogenesis;287
13.6;6. Hes1 Oscillation and Cell Proliferation in Cultured Cells;289
13.7;7. Hes1 Oscillation in ES and NS Cells;292
13.7.1;7.1. Hes1 oscillation in ES cells;292
13.7.2;7.2. Hes1 oscillation in developing mouse brain;293
13.7.3;7.3. Hes1 oscillation in NS cells and the optogenetic control;295
13.8;8. Conclusions and Perspectives;296
13.9;References;297
14;Chapter Eight: Hey bHLH Transcription Factors;302
14.1;1. Introduction;303
14.2;2. Notch Signaling and Crosstalk with Other Pathways;304
14.2.1;2.1. Tgfß/Bmp signaling induces Hey genes;305
14.2.2;2.2. CoupTF-II and Hif1 control cardiovascular Hey expression;306
14.3;3. Interaction Partners of Hey Proteins;307
14.3.1;3.1. Interaction with cofactors;307
14.3.2;3.2. Interaction with other transcription factors;307
14.4;4. Downstream Targets of Hey Proteins;310
14.5;5. Hey Proteins in Heart Development and Disease;311
14.5.1;5.1. Hey genes in adult cardiac disease;315
14.6;6. Hey Proteins in Vascular Development;315
14.6.1;6.1. Role of Hey2 in smooth muscle cells during vascular injury;318
14.7;7. Control of Myogenesis and Muscle Stem Cells;318
14.8;8. Bone Development and Homeostasis;319
14.9;9. Hey Proteins Control Neural Development;321
14.10;10. Hey Functions in Ear Development;322
14.11;11. Immune Functions of Hey Proteins;322
14.12;12. Hey Genes in Cancer;323
14.12.1;12.1. An oncogenic HEY1-NCOA2 fusion protein;323
14.12.2;12.2. Deregulated Hey genes in diverse malignancies;323
14.13;13. Conclusion;324
14.14;References;325
15;Chapter Nine: Stra13 and Sharp-1, the Non-Grouchy Regulators of Development and Disease;334
15.1;1. Introduction;335
15.2;2. Mechanisms of Transcriptional Repression;335
15.3;3. Embryonic and Adult Tissue Expression;337
15.4;4. Roles in Differentiation and Development;339
15.4.1;4.1. Musculoskeletal system;339
15.4.2;4.2. Metabolism;341
15.4.3;4.3. Immune system;342
15.5;5. Deregulation of Stra13 and Sharp-1 in Cancer;343
15.5.1;5.1. Roles in cell cycle arrest senescence;343
15.5.2;5.2. Apoptosis;346
15.5.3;5.3. Hypoxia signaling and DNA repair;346
15.6;6. Conclusion;347
15.7;References;348
16;Chapter Ten: DEC1/STRA13/SHARP2 and DEC2/SHARP1 Coordinate Physiological Processes, Including Circadian Rhythms in Respon...;356
16.1;1. Introduction;357
16.2;2. Structures of DEC1 and DEC2;358
16.2.1;2.1. Primary structures of DEC1 and DEC2 proteins;358
16.2.2;2.2. Genomic structure of Dec1 and Dec2;361
16.3;3. Tissue Distribution and Circadian Expression of Dec1 and Dec2;362
16.4;4. Role of DEC1 and DEC2 in Molecular Clocks;364
16.4.1;4.1. Molecular clock system;364
16.4.2;4.2. Molecular mechanisms involved in DEC activity in the clocks;366
16.4.3;4.3. Resetting of the clocks by DEC;367
16.4.4;4.4. Effects of DEC deficiency on circadian rhythms;368
16.5;5. Mechanisms of DEC1 and DEC2 Actions;369
16.5.1;5.1. Transcriptional repression by direct DNA binding;369
16.5.2;5.2. Transcriptional regulation by protein-protein interaction with other transcription factors;370
16.5.2.1;5.2.1. Hypoxia-inducible factor-1a;370
16.5.2.2;5.2.2. Myoblast determination protein;370
16.5.2.3;5.2.3. Nuclear receptor retinoid X receptor;370
16.5.2.4;5.2.4. Specificity protein 1;371
16.5.2.5;5.2.5. Other factors;371
16.5.3;5.3. Structure-function relationship in DEC proteins;372
16.6;6. Regulatory Factors for Dec1 and Dec2 Expression;372
16.6.1;6.1. Transcription factors;376
16.6.1.1;6.1.1. Clock proteins;376
16.6.1.2;6.1.2. Hypoxia-inducible factor-1;376
16.6.1.3;6.1.3. Nuclear receptors;376
16.6.1.4;6.1.4. Other transcription factors;377
16.6.2;6.2. Growth factors, hormones, and autacoids;378
16.6.3;6.3. Cytokines;380
16.6.4;6.4. Nutrients;380
16.6.5;6.5. Environmental stimuli;381
16.7;7. Perspectives;381
16.8;Acknowledgments;382
16.9;References;382
17;Index;390
18;Color Plate;400

Leseproben

Chapter One Molecular and Cellular Regulation of Skeletal Myogenesis
Glenda Comai; Shahragim Tajbakhsh1    Stem Cells and Development, CNRS URA 2578, Department of Developmental & Stem Cell Biology, Institut Pasteur, Paris, France
1 Corresponding author: email address: [e-mail] Abstract
Since the seminal discovery of the cell-fate regulator Myod, studies in skeletal myogenesis have inspired the search for cell-fate regulators of similar potential in other tissues and organs. It was perplexing that a similar transcription factor for other tissues was not found; however, it was later discovered that combinations of molecular regulators can divert somatic cell fates to other cell types. With the new era of reprogramming to induce pluripotent cells, the myogenesis paradigm can now be viewed under a different light. Here, we provide a short historical perspective and focus on how the regulation of skeletal myogenesis occurs distinctly in different scenarios and anatomical locations. In addition, some interesting features of this tissue underscore the importance of reconsidering the simple-minded view that a single stem cell population emerges after gastrulation to assure tissuegenesis. Notably, a self-renewing long-term Pax7 + myogenic stem cell population emerges during development only after a first wave of terminal differentiation occurs to establish a tissue anlagen in the mouse. How the future stem cell population is selected in this unusual scenario will be discussed. Recently, a wealth of information has emerged from epigenetic and genome-wide studies in myogenic cells. Although key transcription factors such as Pax3, Pax7, and Myod regulate only a small subset of genes, in some cases their genomic distribution and binding are considerably more promiscuous. This apparent nonspecificity can be reconciled in part by the permissivity of the cell for myogenic commitment, and also by new roles for some of these regulators as pioneer transcription factors acting on chromatin state. Keywords Stem/progenitor Skeletal muscle Transcription factor Genetic regulation 1 Introduction
The discovery of Myod in 1987 was a landmark step in our understanding of the processes leading to the acquisition of cell fates—the ectopic expression of a single transcription factor converted many nonmuscle cells to skeletal muscle (Davis, Weintraub, & Lassar, 1987). What followed was perplexing, as researchers failed to identify a similar single potent transcription factor in other tissues, until combinations of transcription factors were identified that had similar cell-fate transforming capabilities from fibroblasts or other adult cell types (Han et al., 2012; Huang et al., 2011; Ieda et al., 2010; Marro et al., 2011; Pang et al., 2011; Sekiya & Suzuki, 2011; Szabo et al., 2010; Vierbuchen et al., 2010; Zhou et al., 2008). More recently, this historical loop was closed following the seminal discovery by Yamanaka that a handful of transcription factors can reprogram adult committed cells to the pluripotent embryonic state (Takahashi & Yamanaka, 2006). These findings raised other issues regarding the permissivity of some cells to conversion, as well as efficacy. It is now clear that the state of the chromatin plays a critical role in defining cell-fate conversion, particularly in those cells that were refractory to myogenic conversion by Myod. Although Myod proved to be potent to initiate the myogenic program, strangely, one such transcription factor was not enough to assure skeletal myogenesis in vertebrates. The closely related genes Myf5, Mrf4 were identified subsequently as determination genes acting in the progeny of stem cells—the muscle progenitor cells—to establish myogenic fate, whereas the related myogenic regulatory factor (Mrf) Myogenin (Myog) drives myogenic differentiation along with Mrf4. Muscle stem cell specification is driven by upstream factors, Pax3/Pax7 in the trunk, and Tbx1/Pitx2 in the head. This review will highlight recent findings and attempt to link them with initial studies on the functional role of the Mrfs. Specifically, four major axes will be developed: (1) similarities and differences between the Mrfs and speculations on why four potent transcription factors are necessary to govern myogenesis; (2) the link between stem cells and their progeny where Mrfs effect their functions in different anatomical locations; (3) challenges in the fields of transdifferentiation and reprogramming seeking to treat muscle disorders; and (4) new mechanistic insights emerging from genome-wide studies into the spatiotemporal control of myogenesis. 2 Molecular Features of the Mrfs
2.1 Mrfs at the nodal point of cell identity—similarities and differences
Mrfs are class II bHLH transcription factors (Murre et al., 1994) that are structurally highly similar, each containing three conserved domains: a transactivation domain in the amino terminal region including a histidine/cysteine (H/C)-rich domain, a bHLH in the central region, and an amphipathic a-helix domain (helix III) in the carboxy terminal transactivation domain (see Singh & Dilworth, 2013). The HLH domains (helix I and II) are required for heterodimerization with ubiquitously expressed class I bHLH E-proteins (HEB/HTF4, E2-2/ITF-2, E12 and E47) (Conway, Pin, Kiernan, & Merrifield, 2004; Henthorn, Kiledjian, & Kadesch, 1990; Lassar et al., 1991; Murre, McCaw, & Baltimore, 1989; Murre, McCaw, Vaessin, et al., 1989; Parker, Perry, Fauteux, Berkes, & Rudnicki, 2006). The basic domain, which is also a-helical, acts as a sequence-specific DNA-binding domain that recognizes the E-box consensus sequence (CANNTG) present in the regulatory region of muscle-specific genes (Blackwell & Weintraub, 1990; Davis, Cheng, Lassar, & Weintraub, 1990; Lassar et al., 1989). A conserved “muscle recognition motif” or “myogenic code” composed of the amino acids AT and K (alanine–threonine within the basic domain, followed by lysine in the junction with helix-I) distinguishes the Mrfs from all the other bHLH transcription factors. These three amino acids confer the ability to activate muscle-specific genes by either interacting with cofactors, or inducing conformational change, or both (Black, Molkentin, & Olson, 1998; Brennan, Chakraborty, & Olson, 1991; Davis et al., 1990; Molkentin, Black, Martin, & Olson, 1995). These amino acid motifs, when substituted into the corresponding sequence of the nonmyogenic bHLH protein E12 are sufficient to confer myogenic potential (Davis & Weintraub, 1992). Myod requires a minimum of two paired E-boxes or an E-box plus a site for a cooperative coactivator (such as Mef2, Sp1, or Pbx and Meis) for activation of reporters in vitro (Biesiada, Hamamori, Kedes, & Sartorelli, 1999; Knoepfler et al., 1999; Molkentin et al., 1995; Sartorelli, Webster, & Kedes, 1990; Weintraub, Davis, Lockshon, & Lassar, 1990). Therefore, dimer formations (Myod–Myod or Myod–coactivator) are crucial for establishing a stable complex with DNA, possibly through induced conformational changes (see Tapscott, 2005). Mef2 family members are expressed in most tissues but are not capable of directing skeletal muscle differentiation in the absence of Mrfs (Molkentin et al., 1995). However, in the promoters and enhancers of muscle-specific genes, E-boxes and Mef2-binding sites are often located in close proximity to one another (Wasserman & Fickett, 1998), and Mef2 proteins and Myod can synergistically accelerate skeletal muscle differentiation in culture (Black et al., 1998; Molkentin et al., 1995; Penn, Bergstrom, Dilworth, Bengal, & Tapscott, 2004). The AT residues appear to be required to mediate the cooperativity between Mrfs and Mef2 proteins to activate muscle genes (Black et al., 1998; Molkentin et al., 1995). Having presumably evolved from a single ancestral invertebrate gene following two rounds of duplication (Atchley, Fitch, & Bronner-Fraser, 1994; Yuan, Zhang, Liu, Luan, & Hu, 2003), the question is why are four different Mrfs required to establish vertebrate muscles. Within their bHLH domains, amino acid sequences have remained largely unchanged during evolution from nematodes to human (Atchley et al., 1994; Zhao, Yu, Huang, & Liu, 2014). In contrast, upstream and downstream of this highly conserved DNA-binding region, considerable differences in sequence become apparent, and they seem to have diverged under positive selection during evolution (Zhao et al., 2014). Therefore, functional differences between the individual Mrfs can be explained in part by their different structural characteristics as explained below. First, generation of chimeric Mrfs by domain swapping experiments in vitro have demonstrated that the N- and C-terminal domains of Myf5 and Myod are interchangeable for the activation of gene expression during myoblast proliferation but not in differentiation culture conditions. In this...