scholarly journals An Examination of the Role of Transcriptional and Posttranscriptional Regulation in Rhabdomyosarcoma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Alexander J. Hron ◽  
Atsushi Asakura
Keyword(s):  
Skeletal Muscle ◽  
Soft Tissue ◽  
Posttranscriptional Regulation ◽  
Progenitor Cell ◽  
Treatment Options ◽  
Soft Tissue Tumors ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Proteins

Rhabdomyosarcoma (RMS) is an aggressive family of soft tissue tumors that most commonly manifests in children. RMS variants express several skeletal muscle markers, suggesting myogenic stem or progenitor cell origin of RMS. In this review, the roles of both recently identified and well-established microRNAs in RMS are discussed and summarized in a succinct, tabulated format. Additionally, the subtypes of RMS are reviewed along with the involvement of basic helix-loop-helix (bHLH) proteins, Pax proteins, and microRNAs in normal and pathologic myogenesis. Finally, the current and potential future treatment options for RMS are outlined.

scholarly journals Molecular Distinction between Specification and Differentiation in the Myogenic Basic Helix-Loop-Helix Transcription Factor Family

2001 ◽  
Vol 21 (7) ◽  
pp. 2404-2412 ◽  
Author(s):  
Donald A. Bergstrom ◽  
Stephen J. Tapscott
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Molecular Basis ◽  
Alpha Helix ◽  
Endogenous Gene ◽  
Transcriptional Activation Domain ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Muscle Genes ◽  
Bhlh Proteins

ABSTRACT The myogenic basic helix-loop-helix (bHLH) proteins regulate both skeletal muscle specification and differentiation: MyoD and Myf5 establish the muscle lineage, whereas myogenin mediates differentiation. Previously, we demonstrated that MyoD was more efficient than myogenin at initiating the expression of skeletal muscle genes, and in this study we present the molecular basis for this difference. A conserved amphipathic alpha-helix in the carboxy terminus of the myogenic bHLH proteins has distinct activities in MyoD and myogenin: the MyoD helix facilitates the initiation of endogenous gene expression, whereas the myogenin helix functions as a general transcriptional activation domain. Thus, the alternate use of a similar motif for gene initiation and activation provides a molecular basis for the distinction between specification and differentiation within the myogenic bHLH gene family.

Determination versus differentiation and the MyoD family of transcription factors

1995 ◽  
Vol 73 (9-10) ◽  
pp. 723-732 ◽  
Author(s):  
Lynn A. Megeney ◽  
Michael A. Rudnicki
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Sequence Homology ◽  
Expression Patterns ◽  
Myogenic Regulatory Factors ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

The myogenic regulatory factors (MRFs) form a family of basic helix–loop–helix transcription factors consisting of Myf-5, MyoD, myogenin, and MRF4. The MRFs play key regulatory roles in the development of skeletal muscle during embryogenesis. Sequence homology, expression patterns, and genetargeting experiments have revealed a two-tiered subclassification within the MRF family. Myf-5 and MyoD are more homologous to one another than to the others, are expressed in myoblasts before differentiation, and are required for the determination or survival of muscle progenitor cells. By contrast, myogenin and MRF4 are more homologous to one another than to the others and are expressed upon differentiation, and myogenin is required in vivo as a differentiation factor while the role of MRF4 remains unclear. On this basis, MyoD and Myf-5 are classified as primary MRFs, as they are required for the determination of myoblasts, and myogenin and MRF4 are classified as secondary MRFs, as they likely function during terminal differentiation.Key words: MyoD, Myf-5, myogenin, MRF4, skeletal muscle.

Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2

Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4272-4281 ◽  
Author(s):  
Miranda Buitenhuis ◽  
Hanneke W. M. van Deutekom ◽  
Liesbeth P. Verhagen ◽  
Anders Castor ◽  
Sten Eirik W. Jacobsen ◽  
...  
Keyword(s):  
Critical Role ◽  
Ectopic Expression ◽  
Constitutive Expression ◽  
Retroviral Transduction ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Cd34 Cells ◽  
Final Maturation ◽  
Inhibitor Of Dna Binding

Abstract Inhibitor of DNA binding (Id) proteins function as inhibitors of members of the basic helix-loop-helix family of transcription factors and have been demonstrated to play an important role in regulating lymphopoiesis. However, the role of these proteins in regulation of myelopoiesis is currently unclear. In this study, we have investigated the role of Id1 and Id2 in the regulation of granulopoiesis. Id1 expression was initially up-regulated during early granulopoiesis, which was then followed by a decrease in expression during final maturation. In contrast, Id2 expression was up-regulated in terminally differentiated granulocytes. In order to determine whether Id expression plays a critical role in regulating granulopoiesis, Id1 and Id2 were ectopically expressed in CD34+ cells by retroviral transduction. Our experiments demonstrate that constitutive expression of Id1 inhibits eosinophil development, whereas in contrast neutrophil differentiation was modestly enhanced. Constitutive Id2 expression accelerates final maturation of both eosinophils and neutrophils, whereas inhibition of Id2 expression blocks differentiation of both lineages. Transplantation of β2-microglobulin-/- nonobese diabetic severe combined immunodeficient (NOD/SCID) mice with CD34+ cells ectopically expressing Id1 resulted in enhanced neutrophil development, whereas ectopic expression of Id2 induced both eosinophil and neutrophil development. These data demonstrate that both Id1 and Id2 play a critical, although differential role in granulopoiesis.

scholarly journals Inhibition of Tcf3 Binding by I-mfa Domain Proteins

2001 ◽  
Vol 21 (5) ◽  
pp. 1866-1873 ◽  
Author(s):  
Lauren Snider ◽  
Hilary Thirlwell ◽  
Jeffrey R. Miller ◽  
Randall T. Moon ◽  
Mark Groudine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Wnt Signaling ◽  
Binding Sites ◽  
Ectopic Expression ◽  
Wnt Signaling Pathway ◽  
Developmental Pathways ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Dorsal Axis ◽  
Bhlh Proteins

ABSTRACT We have determined that I-mfa, an inhibitor of several basic helix-loop-helix (bHLH) proteins, and XIC, a Xenopusortholog of human I-mf domain-containing protein that shares a highly conserved cysteine-rich C-terminal domain with I-mfa, inhibit the activity and DNA binding of the HMG box transcription factor XTcf3. Ectopic expression of I-mfa or XIC in early Xenopus embryos inhibited dorsal axis specification, the expression of the Tcf3/β-catenin-regulated genessiamois and Xnr3, and the ability of β-catenin to activate reporter constructs driven by Lef/Tcf binding sites. I-mfa domain proteins can regulate both the Wnt signaling pathway and a subset of bHLH proteins, possibly coordinating the activities of these two critical developmental pathways.

Scleraxis: a basic helix-loop-helix protein that prefigures skeletal formation during mouse embryogenesis

Development ◽  
1995 ◽  
Vol 121 (4) ◽  
pp. 1099-1110 ◽  
Author(s):  
P. Cserjesi ◽  
D. Brown ◽  
K.L. Ligon ◽  
G.E. Lyons ◽  
N.G. Copeland ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Expression Pattern ◽  
Consensus Sequence ◽  
Cell Types ◽  
Cell Type ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box ◽  
Cell Type Specific ◽  
Bhlh Proteins

Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to regulate growth and differentiation of numerous cell types. Cell-type-specific bHLH proteins typically form heterodimers with ubiquitous bHLH proteins, such as E12, and bind a DNA consensus sequence known as an E-box. We used the yeast two-hybrid system to screen mouse embryo cDNA libraries for cDNAs encoding novel cell-type-specific bHLH proteins that dimerize with E12. One of the cDNAs isolated encoded a novel bHLH protein, called scleraxis. During mouse embryogenesis, scleraxis transcripts were first detected between day 9.5 and 10.5 post coitum (p.c.) in the sclerotome of the somites and in mesenchymal cells in the body wall and limb buds. Subsequently, scleraxis was expressed at high levels within mesenchymal precursors of the axial and appendicular skeleton and in cranial mesenchyme in advance of chondrogenesis; its expression pattern in these cell types foreshadowed the developing skeleton. Prior to formation of the embryonic cartilaginous skeleton, scleraxis expression declined to low levels. As development proceeded, high levels of scleraxis expression became restricted to regions where cartilage and connective tissue formation take place. Scleraxis bound the E-box consensus sequence as a heterodimer with E12 and activated transcription of a reporter gene linked to its DNA-binding site. The expression pattern, DNA-binding properties and transcriptional activity of scleraxis suggest that it is a regulator of gene expression within mesenchymal cell lineages that give rise to cartilage and connective tissue.

The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo

Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2945-2954 ◽  
Author(s):  
A.A. Gershon ◽  
J. Rudnick ◽  
L. Kalam ◽  
K. Zimmerman
Keyword(s):  
Neuronal Differentiation ◽  
Normal Development ◽  
Early Embryo ◽  
Neural Plate ◽  
Neural Progenitors ◽  
Expression Domain ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Early Neurogenesis

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

scholarly journals Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 102-111 ◽  
Author(s):  
T Hoang ◽  
E Paradis ◽  
G Brady ◽  
F Billia ◽  
K Nakahara ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Single Cells ◽  
Hematopoietic Cells ◽  
Erythroid Differentiation ◽  
Mrna Levels ◽  
Monocytic Differentiation ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Opposing Effects

Abstract The SCL gene (also called Tal-1 or TCL5) was identified because of its association with chromosomal translocations in childhood T-cell lymphoid leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can function as a transcriptional activator or repressor. In the adult, SCL expression is restricted to hematopoietic cells and tissues, but its function in the process of lineage commitment is unknown. The present study was designed to address the role of SCL in hematopoietic cell differentiation. SCL expression was determined in primary hematopoietic cells through the screening of cDNA samples obtained by reverse transcription-polymerase chain reaction (RT-PCR) from single cells at different stages of differentiation. SCL RNA expression was highest in bipotential and committed erythroid precursors and diminished with subsequent maturation to proerythroblasts and normoblasts. In contrast, SCL mRNA was low to undetectable in precursors of granulocytes and monocytes and their maturing progeny. The same pattern of expression was observed after erythroid or monocytic differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained elevated during erythroid differentiation and were downregulated with monocytic differentiation. Accordingly, TF-1 was chosen as a model to investigate the functional significance of this divergent pattern of SCL expression in the two lineages. Four independent clones stably transfected with an SCL expression vector exhibited enhanced spontaneous and delta-aminolevulinic acid-induced erythroid differentiation as measured by glycophorin expression and hemoglobinization, consistent with the view that SCL is a positive regulator of erythroid differentiation. Furthermore, constitutive SCL expression interfered with monocytic differentiation, as assessed by the generation of adherent cells and the expression of Fc gamma RII in response to TPA. These results suggest that the downregulation of SCL may be required for monocytic differentiation.

Adipocyte-rich CTNNB1-mutated Intramuscular Gardner Fibroma Progressing to Desmoid Fibromatosis

2020 ◽  
pp. 109352662096880
Author(s):  
Andrea Bakker ◽  
Jonathan C Slack ◽  
Mara Caragea ◽  
Kyle C Kurek ◽  
Marie-Anne Bründler
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Tumor ◽  
Soft Tissue Tumors ◽  
Molecular Testing ◽  
Tissue Mass ◽  
Desmoid Fibromatosis ◽  
Benign Soft Tissue Tumor ◽  
First Time ◽  
Generation Sequencing

Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called “GF-DF sequence”) is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear β-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF–DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF–DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.

The Role of Ultrasound in the Diagnosis of Soft Tissue Tumors

2020 ◽  
Vol 24 (02) ◽  
pp. 135-155
Author(s):  
Maria Pilar Aparisi Gómez ◽  
Costantino Errani ◽  
Radhesh Lalam ◽  
Violeta Vasilevska Nikodinovska ◽  
Stefano Fanti ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Benign Lesion ◽  
Soft Tissue Tumors ◽  
Resonance Imaging ◽  
Benign Lesions ◽  
Tumor Center ◽  
Soft Tissue Masses ◽  
Magnetic Resonance Imaging Mri ◽  
Superficial Soft Tissue

AbstractThe vast majority of soft tissue masses are benign. Benign lesions such as superficial lipomas and ganglia are by far the most common soft tissue masses and can be readily identified and excluded on ultrasound (US). US is an ideal triaging tool for superficial soft tissue masses. Compared with magnetic resonance imaging (MRI), High-resolution US is inexpensive, readily available, well tolerated, and safe. It also allows the radiologist to interact with the patient as a clinician. In this review, we describe and illustrate the lesions with typical (diagnostic) US features. When the appearances of the lesion are not typical as expected for a benign lesion, lesions are deep or large, or malignancy is suspected clinically, MRI and biopsy are needed. The management of suspicious soft tissue tumors has to be carefully planned by a multidisciplinary team involving specialized surgeons and pathologists at a tumor center.

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