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.

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 Intramolecular Regulation of MyoD Activation Domain Conformation and Function

1998 ◽  
Vol 18 (9) ◽  
pp. 5478-5484 ◽  
Author(s):  
Jing Huang ◽  
Hal Weintraub ◽  
Larry Kedes
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Helix Loop Helix ◽  
Dna Binding Specificity ◽  
E Box ◽  
And Function ◽  
Bhlh Proteins ◽  
Basic Region

ABSTRACT The MyoD family of basic helix-loop-helix (bHLH) proteins is required for myogenic determination and differentiation. The basic region carries the myogenic code and DNA binding specificity, while the N terminus contains a potent transcriptional activation domain. Myogenic activation is abolished when the basic region, bound to a myogenic E box, carries a mutation of Ala-114. It has been proposed that DNA binding of the MyoD basic region leads to recruitment of a recognition factor that unmasks the activation domain. Here we demonstrate that an A114N mutant exhibits an altered conformation in the basic region and that this local conformational difference can lead to a more global change affecting the conformation of the activation domain. This suggests that the deleterious effects of this class of mutations may result directly from defective conformation. Thus, the activation domain is unmasked only upon DNA binding by the correct basic region. Such a coupled conformational relationship may have evolved to restrict myogenic specificity to a small number of bHLH proteins among many with diverse functions yet with DNA binding specificities known to be similar.

scholarly journals A chimeric enhancer-of-split transcriptional activator drives neural development and achaete-scute expression.

1997 ◽  
Vol 17 (8) ◽  
pp. 4355-4362 ◽  
Author(s):  
G Jiménez ◽  
D Ish-Horowicz
Keyword(s):  
Neural Development ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Wild Type ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Helix Loop Helix ◽  
Inhibition Process ◽  
Bhlh Proteins ◽  
Enhancer Of Split

Drosophila melanogaster neurogenesis requires the opposing activities of two sets of basic helix-loop-helix (bHLH) proteins: proneural proteins, which confer on cells the ability to become neural precursors, and the Enhancer-of-split [E(spl)] proteins, which restrict such potential as part of the lateral inhibition process. Here, we test if E(spl) proteins function as promoter-bound repressors by examining the effects on neurogenesis of an E(spl) derivative containing a heterologous transcriptional activation domain [E(spl) m7Act (m7Act)]. In contrast to the wild-type E(spl) proteins, m7Act efficiently induces neural development, indicating that it binds to and activates target genes normally repressed by E(spl). Mutations in the basic domain disrupt m7Act activity, suggesting that its effects are mediated through direct DNA binding. m7Act causes ectopic transcription of the proneural achaete and scute genes. Our results support a model in which E(spl) proteins normally regulate neurogenesis by direct repression of genes at the top of the neural determination pathway.

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.

scholarly journals mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization.

1992 ◽  
Vol 12 (2) ◽  
pp. 817-827 ◽  
Author(s):  
C Roman ◽  
A G Matera ◽  
C Cooper ◽  
S Artandi ◽  
S Blain ◽  
...  
Keyword(s):  
Dna Binding ◽  
Heavy Chain ◽  
Leucine Zipper ◽  
Immunoglobulin Heavy Chain ◽  
Functional Roles ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Individual ◽  
Bhlh Proteins ◽  
High Degree

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

scholarly journals MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206

2006 ◽  
Vol 175 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Miriam I. Rosenberg ◽  
Sara A. Georges ◽  
Amy Asawachaicharn ◽  
Erwin Analau ◽  
Stephen J. Tapscott
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Cell Types ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Distinct Cell ◽  
Muscle Genes ◽  
Suppression Of Gene Expression ◽  
Dystrophin Protein

Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes. To characterize a mechanism of MyoD-mediated suppression of gene expression, we investigated two genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD, follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206. These findings demonstrate that MyoD, in addition to activating muscle-specific genes, induces miRNAs that repress gene expression during skeletal muscle differentiation.

A genome-wide identification and classification of basic helix-loop-helix genes in the jewel wasp, Nasonia vitripennis (Hymenoptera: Pteromalidae)

Genome ◽  
2014 ◽  
Vol 57 (10) ◽  
pp. 525-536 ◽  
Author(s):  
Xiao-Ting Liu ◽  
Yong Wang ◽  
Xu-Hua Wang ◽  
Xia-Fang Tao ◽  
Qin Yao ◽  
...  
Keyword(s):  
Heart Development ◽  
Family Members ◽  
Insect Species ◽  
Structural Domain ◽  
Nasonia Vitripennis ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
A Genome ◽  
Bhlh Genes ◽  
Bhlh Proteins

Basic helix-loop-helix (bHLH) proteins are highly conserved DNA-binding transcription factors of a large superfamily. Animal bHLH proteins play important regulatory roles in various developmental processes such as neurogenesis, myogenesis, heart development, and hematopoiesis. The jewel wasp (Nasonia vitripennis) is a good model organism of hymenoptera insects for studies of developmental and evolutionary genetics. In this study, we identified 48 bHLH genes in the genome of N. vitripennis. According to phylogenetic analysis, based on N. vitripennis bHLH (NvbHLH) motif sequences and structural domain distribution in their full-length protein sequences, the identified NvbHLH genes were classified into 36 bHLH families with 19, 12, 9, 1, 6, and 1 member(s) in groups A, B, C, D, E, and F, respectively. Our classification to the identified NvbHLH family members confirms GenBank annotations for 21 of the 48 NvbHLH proteins and provides useful information for further characterization and annotation of the remaining 27 NvbHLH proteins. Compared to other insect species, N. vitripennis has the lowest number of bHLH family members. No NvbHLH members have been found in the families Net, MyoRa, and PTFa, while all other insect species have at least one member in each of the families. These data constitute a solid basis for further investigations into the functions of bHLH proteins in developmental regulation of N. vitripennis.

scholarly journals MondoA, a Novel Basic Helix-Loop-Helix–Leucine Zipper Transcriptional Activator That Constitutes a Positive Branch of a Max-Like Network

2000 ◽  
Vol 20 (23) ◽  
pp. 8845-8854 ◽  
Author(s):  
Andrew N. Billin ◽  
Alanna L. Eilers ◽  
Kathryn L. Coulter ◽  
Jennifer S. Logan ◽  
Donald E. Ayer
Keyword(s):  
Transcriptional Activation ◽  
Nuclear Export ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
Functional Characterization ◽  
Nuclear Accumulation ◽  
Cytoplasmic Localization ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

ABSTRACT Max is a common dimerization partner for a family of transcription factors (Myc, Mad [or Mxi]), and Mnt [or Rox] proteins) that regulate cell growth, proliferation, and apoptosis. We recently characterized a novel Max-like protein, Mlx, which interacts with Mad1 and Mad4. Here we describe the cloning and functional characterization of a new family of basic helix-loop-helix–leucine zipper heterodimeric partners for Mlx termed the Mondo family. MondoA forms homodimers weakly and does not interact with Max or members of the Myc or Mad families. MondoA and Mlx associate in vivo, and surprisingly, they are localized primarily to the cytoplasm of cultured mammalian cells. Treatment of cells with the nuclear export inhibitor leptomycin B results in the nuclear accumulation of MondoA and Mlx, demonstrating that they shuttle between the cytoplasmic and nuclear compartments rather than having exclusively cytoplasmic localization. MondoA preferentially forms heterodimers with Mlx, and this heterocomplex can bind to, and activate transcription from, CACGTG E-boxes when targeted to the nucleus via a heterologous nuclear localization signal. The amino termini of the Mondo proteins are highly conserved among family members and contain separable and autonomous cytoplasmic localization and transcription activation domains. Therefore, Mlx can mediate transcriptional repression in conjunction with the Mad family and can mediate transcriptional activation via the Mondo family. We propose that Mlx, like Max, functions as the center of a transcription factor network.

Sign in / Sign up

Export Citation Format

Share Document