scholarly journals Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

1995 ◽  
Vol 15 (5) ◽  
pp. 2707-2718 ◽  
Author(s):  
P S Naidu ◽  
D C Ludolph ◽  
R Q To ◽  
T J Hinterberger ◽  
S F Konieczny
Keyword(s):  
Molecular Mechanisms ◽  
Muscle Development ◽  
Expression Patterns ◽  
Proximal Promoter ◽  
Sufficient Information ◽  
Specific Response ◽  
Specific Expression ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box

The basic helix-loop-helix muscle regulatory factor (MRF) gene family encodes four distinct muscle-specific transcription factors known as MyoD, myogenin, Myf-5, and MRF4. These proteins represent key regulatory factors that control many aspects of skeletal myogenesis. Although the MRFs often exhibit overlapping functional activities, their distinct expression patterns during embryogenesis suggest that each protein plays a unique role in controlling aspects of muscle development. As a first step in determining how MRF4 gene expression is developmentally regulated, we examined the ability of the MRF4 gene to be expressed in a muscle-specific fashion in vitro. Our studies show that the proximal MRF4 promoter contains sufficient information to direct muscle-specific expression. Located within the proximal promoter are a single MEF2 site and E box that are required for maximum MRF4 expression. Mutation of the MEF2 site or E box severely impairs the ability of this promoter to produce a muscle-specific response. In addition, the MEF2 site and E box function in concert to synergistically activate the MRF4 gene in nonmuscle cells coexpressing MEF2 and myogenin proteins. Thus, the MRF4 promoter is regulated by the MEF2 and basic helix-loop-helix MRF protein family through a cross-regulatory circuitry. Surprisingly, the MRF4 promoter itself is not transactivated by MRF4, suggesting that this MRF gene is not subject to an autoregulatory pathway as previously implied by other studies. Understanding the molecular mechanisms regulating expression of each MRF gene is central to fully understanding how these factors control developmental events.

scholarly journals Genome-Wide Analysis of Basic Helix–Loop–Helix Superfamily Members Reveals Organization and Chilling-Responsive Patterns in Cabbage (Brassica oleracea var. capitata L.)

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 914
Author(s):  
Shan ◽  
Zhang ◽  
Yu ◽  
Wang ◽  
Li ◽  
...  
Keyword(s):  
Brassica Oleracea ◽  
Expression Profiles ◽  
Phylogenetic Analyses ◽  
Chilling Stress ◽  
Expression Patterns ◽  
Comprehensive Analysis ◽  
Bhlh Transcription Factor ◽  
Specific Expression ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Basic helix–loop–helix (bHLH) transcription factor (TF) family is commonly found in eukaryotes, which is one of the largest families of regulator proteins. It plays an important role in plant growth and development, as well as various biotic and abiotic stresses. However, a comprehensive analysis of the bHLH family has not been reported in Brassica oleracea. In this study, we systematically describe the BobHLHs in the phylogenetic relationships, expression patterns in different organs/tissues, and in response to chilling stress, and gene and protein characteristics. A total of 234 BobHLH genes were identified in the B. oleracea genome and were further clustered into twenty-three subfamilies based on the phylogenetic analyses. A large number of BobHLH genes were unevenly located on nine chromosomes of B. oleracea. Analysis of RNA-Seq expression profiles revealed that 21 BobHLH genes exhibited organ/tissue-specific expression. Additionally, the expression of six BobHLHs (BobHLH003, -048, -059, -093, -109, and -148) were significantly down-regulated in chilling-sensitive cabbage (CS-D9) and chilling-tolerant cabbage (CT-923). At 24h chilling stress, BobHLH054 was significantly down-regulated and up-regulated in chilling-treated CS-D9 and CT-923. Conserved motif characterization and exon/intron structural patterns showed that BobHLH genes had similar structures in the same subfamily. This study provides a comprehensive analysis of BobHLH genes and reveals several candidate genes involved in chilling tolerance of B. oleracea, which may be helpful to clarify the roles of bHLH family members and understand the regulatory mechanisms of BobHLH genes in response to the chilling stress of cabbage.

scholarly journals PU.1/Pip and Basic Helix Loop Helix Zipper Transcription Factors Interact With Binding Sites in the CD20 Promoter to Help Confer Lineage- and Stage-Specific Expression of CD20 in B Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 3984-3995 ◽  
Author(s):  
Andreas Himmelmann ◽  
Agostino Riva ◽  
Gaye Lynn Wilson ◽  
Brian P. Lucas ◽  
Claire Thevenin ◽  
...  
Keyword(s):  
B Cell ◽  
Plasma Cells ◽  
Expression Vectors ◽  
Specific Gene ◽  
Cell Stage ◽  
Specific Expression ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box

Abstract CD20 is a B-lineage–specific gene expressed at the pre–B-cell stage of B-cell development that disappears on differentiation to plasma cells. As such, it serves as an excellent paradigm for the study of lineage and developmental stage-specific gene expression. Using in vivo footprinting we identified two sites in the promoter at −45 and −160 that were occupied only in CD20+ B cells. The −45 site is an E box that binds basic helix-loop-helix-zipper proteins whereas the −160 site is a composite PU.1 and Pip binding site. Transfection studies with reporter constructs and various expression vectors verified the importance of these sites. The composite PU.1 and Pip site likely accounts for both lineage and stage-specific expression of CD20 whereas the CD20 E box binding proteins enhance overall promoter activity and may link the promoter to a distant enhancer.

scholarly journals The Evolution of the Neural Basic Helix-Loop-Helix Proteins

2001 ◽  
Vol 1 ◽  
pp. 396-426 ◽  
Author(s):  
Michel Vervoort ◽  
Valerie Ledent
Keyword(s):  
Expression Patterns ◽  
Neural Cells ◽  
Specific Expression ◽  
Neural Fate ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Neuronal Precursors ◽  
Vertebrate Orthologs ◽  
Mature Neurons

Basic Helix-Loop-Helix (bHLH) transcription factors control various aspects of the formation of the nervous system in the metazoans. In Drosophila some bHLH (such as the achaete-scuteatonal, and amos genes) act as proneural genes, directing ectodermal cells toward a neural fate. Their vertebrate orthologs, however, probably do not assume such a neural determination function, but rather control the decision made by neural precursors to generate neurons and not glial cells, as well as the progression of neuronal precursors toward differentiation into mature neurons. The proneural function of Drosophila bHLH genes may be an innovation that occurs in the evolutive lineage that leads to arthropods. In addition, although neural bHLH appear to be involved in the specification of neuronal identities, they probably do not confer by themselves neuronal type-specific properties to the cells. Rather, neural bHLH allow neural cells to correctly interpret specification and positional cues provided by other factors. Although bHLH genes are often expressed in complementary subsets of neural cells and/or expressed sequentially in those cells, the coding regions of the various neural bHLH appear largely interchangeable. We propose that the specific expression patterns have been acquired, following gene duplications, by subfunctional-ization, i.e., the partitioning of ancestral expression patterns among the duplicates and, by extension, we propose that subfunctionalization is a key process to understand the evolution of neural bHLH genes.

scholarly journals Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter.

1991 ◽  
Vol 11 (5) ◽  
pp. 2439-2450 ◽  
Author(s):  
B A French ◽  
K L Chow ◽  
E N Olson ◽  
R J Schwartz
Keyword(s):  
Dna Binding ◽  
Muscle Development ◽  
Specific Expression ◽  
Cis Acting ◽  
Helix Loop Helix ◽  
E Box ◽  
Carg Box ◽  
Actin Promoter ◽  
E Boxes ◽  
Alpha Actin

Recent studies have shown that two genes regulating myogenesis (MyoD and myogenin) are coexpressed with cardiac alpha-actin during early stages of skeletal muscle development. Myogenin and MyoD are members of a family of regulatory proteins which share a helix-loop-helix (HLH) motif required for dimerization and DNA binding. Myogenin and MyoD form heterodimers with the ubiquitous HLH protein E12 which bind cis-acting DNA elements that have an E box (CANNTG) at their core. E boxes are present in the control regions of numerous muscle-specific genes, although their functional importance in regulating many of these genes has not yet been evaluated. In this report we examine the possibility that myogenin (or MyoD) directly transactivates the cardiac alpha-actin promoter. Heterodimers of myogenin and E12 (or MyoD and E12) specifically bound a restriction fragment extending from -200 to -103 relative to the start of cardiac alpha-actin transcription. Methylation interference footprints pinpointed the site of interaction to an E box immediately adjacent to a previously identified CArG box (CArG3). Site-directed mutations to the DNA-binding site revealed that either an intact E box or an intact CArG3 is required for induction of the cardiac alpha-actin promoter in myoblasts and for transactivation by myogenin in cotransfected fibroblasts. However, deletion and substitution experiments indicate that the complex E box/CArG3 element alone does not confer muscle-specific expression to a minimal promoter. These results suggest that direct and indirect pathways involving multiple cis-acting elements mediate the induction of the cardiac alpha-actin promoter by myogenin and MyoD.

scholarly journals The Basic Helix-Loop-Helix, Leucine Zipper Transcription Factor, USF (Upstream Stimulatory Factor), Is a Key Regulator of SF-1 (Steroidogenic Factor-1) Gene Expression in Pituitary Gonadotrope and Steroidogenic Cells

1998 ◽  
Vol 12 (5) ◽  
pp. 714-726 ◽  
Author(s):  
Adrienne N. Harris ◽  
Pamela L. Mellon
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Transcriptional Regulator ◽  
Orphan Nuclear Receptor ◽  
Upstream Stimulatory Factor ◽  
Specific Expression ◽  
Steroidogenic Factor 1 ◽  
Helix Loop Helix ◽  
E Box ◽  
Stimulatory Factor

Abstract Tissue-specific expression of the mammalian FTZ-F1 gene is essential for adrenal and gonadal development and sexual differentiation. The FTZ-F1 gene encodes an orphan nuclear receptor, termed SF-1 (steroidogenic factor-1) or Ad4BP, which is a primary transcriptional regulator of several hormone and steroidogenic enzyme genes that are critical for normal physiological function of the hypothalamic-pituitary-gonadal axis in reproduction. The objective of the current study is to understand the molecular mechanisms underlying transcriptional regulation of SF-1 gene expression in the pituitary. We have studied a series of deletion and point mutations in the SF-1 promoter region for transcriptional activity in αT3–1 and LβT2 (pituitary gonadotrope), CV-1, JEG-3, and Y1 (adrenocortical) cell lines. Our results indicate that maximal expression of the SF-1 promoter in all cell types requires an E box element at −82/−77. This E box sequence (CACGTG) is identical to the binding element for USF (upstream stimulatory factor), a member of the helix-loop-helix family of transcription factors. Studies of the SF-1 gene E box element using gel mobility shift and antibody supershift assays indicate that USF may be a key transcriptional regulator of SF-1 gene expression.

scholarly journals Interpretation of X Chromosome Dose at Sex-lethalRequires Non-E-Box Sites for the Basic Helix-Loop-Helix Proteins SISB and Daughterless

2001 ◽  
Vol 21 (5) ◽  
pp. 1581-1592 ◽  
Author(s):  
Dun Yang ◽  
Hong Lu ◽  
Yong Hong ◽  
Timothy M. Jinks ◽  
Patricia A. Estes ◽  
...  
Keyword(s):  
X Chromosome ◽  
Molecular Mechanisms ◽  
Protein Product ◽  
P Element ◽  
Functional Requirements ◽  
Mobility Shift ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box ◽  
Gel Mobility Shift

ABSTRACT For Drosophila melanogaster flies, sexual fate is determined by the X chromosome number. The basic helix-loop-helix protein product of the X-linked sisterlessB(sisB or scute) gene is a key indicator of the X dose and functions to activate the switch gene Sex-lethal (Sxl) in female (XX), but not in male (XY), embryos. Zygotically expressed sisB and maternal daughterless (da)proteins are known to form heterodimers that bind E-box sites and activate transcription. We examined SISB-Da binding atSxl by using footprinting and gel mobility shift assays and found that SISB-Da binds numerous clustered sites in the establishment promoter SxlPe . Surprisingly, most SISB-Da sites at SxlPe differ from the canonical CANNTG E-box motif. These noncanonical sites have 6-bp CA(G/C)CCG and 7-bp CA(G/C)CTTG cores and exhibit a range of binding affinities. We show that the noncanonical sites can mediate SISB-Da-activated transcription in cell culture. P-element transformation experiments show that these noncanonical sites are essential for SxlPe activity in embryos. Together with previous deletion analysis, the data suggest that the number, affinity, and position of SISB-Da sites may all be important for the operation of the SxlPe switch. Comparisons with other dose-sensitive promoters suggest that threshold responses to diverse biological signals have common molecular mechanisms, with important variations tailored to suit particular functional requirements.

Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter

1991 ◽  
Vol 11 (5) ◽  
pp. 2439-2450
Author(s):  
B A French ◽  
K L Chow ◽  
E N Olson ◽  
R J Schwartz
Keyword(s):  
Dna Binding ◽  
Muscle Development ◽  
Specific Expression ◽  
Cis Acting ◽  
Helix Loop Helix ◽  
E Box ◽  
Carg Box ◽  
Actin Promoter ◽  
E Boxes ◽  
Alpha Actin

Recent studies have shown that two genes regulating myogenesis (MyoD and myogenin) are coexpressed with cardiac alpha-actin during early stages of skeletal muscle development. Myogenin and MyoD are members of a family of regulatory proteins which share a helix-loop-helix (HLH) motif required for dimerization and DNA binding. Myogenin and MyoD form heterodimers with the ubiquitous HLH protein E12 which bind cis-acting DNA elements that have an E box (CANNTG) at their core. E boxes are present in the control regions of numerous muscle-specific genes, although their functional importance in regulating many of these genes has not yet been evaluated. In this report we examine the possibility that myogenin (or MyoD) directly transactivates the cardiac alpha-actin promoter. Heterodimers of myogenin and E12 (or MyoD and E12) specifically bound a restriction fragment extending from -200 to -103 relative to the start of cardiac alpha-actin transcription. Methylation interference footprints pinpointed the site of interaction to an E box immediately adjacent to a previously identified CArG box (CArG3). Site-directed mutations to the DNA-binding site revealed that either an intact E box or an intact CArG3 is required for induction of the cardiac alpha-actin promoter in myoblasts and for transactivation by myogenin in cotransfected fibroblasts. However, deletion and substitution experiments indicate that the complex E box/CArG3 element alone does not confer muscle-specific expression to a minimal promoter. These results suggest that direct and indirect pathways involving multiple cis-acting elements mediate the induction of the cardiac alpha-actin promoter by myogenin and MyoD.

scholarly journals β-Catenin Interacts with MyoD and Regulates Its Transcription Activity

2008 ◽  
Vol 28 (9) ◽  
pp. 2941-2951 ◽  
Author(s):  
Chang-Hoon Kim ◽  
Hannah Neiswender ◽  
Eun Joo Baik ◽  
Wen C. Xiong ◽  
Lin Mei
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activity ◽  
Muscle Development ◽  
Muscle Cells ◽  
Muscle Differentiation ◽  
Canonical Pathway ◽  
Transcription Activity ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box

ABSTRACT Wnt regulation of muscle development is thought to be mediated by the β-catenin-TCF/LEF-dependent canonical pathway. Here we demonstrate that β-catenin, not TCF/LEF, is required for muscle differentiation. We showed that β-catenin interacts directly with MyoD, a basic helix-loop-helix transcription factor essential for muscle differentiation and enhances its binding to E box elements and transcriptional activity. MyoD-mediated transactivation is inhibited in muscle cells when β-catenin is deficient or the interaction between MyoD and β-catenin is disrupted. These results demonstrate that β-catenin is necessary for MyoD function, identifying MyoD as an effector in the Wnt canonical pathway.

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