scholarly journals Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3411-3419 ◽  
Author(s):  
Angelike Stathopoulos ◽  
Michael Levine
Keyword(s):  
Target Genes ◽  
Early Gene ◽  
Bhlh Protein ◽  
Bhlh Transcription Factor ◽  
Gradient System ◽  
Dorsoventral Patterning ◽  
Helix Loop Helix ◽  
Dorsal Pathway ◽  
Toll Signaling ◽  
Toll Receptor

Differential activation of the Toll receptor leads to the formation of a broad Dorsal nuclear gradient that specifies at least three patterning thresholds of gene activity along the dorsoventral axis of precellular embryos. We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling. Pelle functions downstream of Toll to release Dorsal from the Cactus inhibitor. Twist is an immediate-early gene that is activated upon entry of Dorsal into nuclei. Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling. These studies suggest that an anteroposterior gradient of Pelle kinase activity is sufficient to generate all known Toll-Dorsal patterning thresholds and that Twist can function as a gradient morphogen to establish at least two distinct dorsoventral patterning thresholds. We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis.

scholarly journals Basic Helix-Loop-Helix (bHLH) Transcription Factors Regulate a Wide Range of Functions in Arabidopsis

2021 ◽  
Vol 22 (13) ◽  
pp. 7152
Author(s):  
Yaqi Hao ◽  
Xiumei Zong ◽  
Pan Ren ◽  
Yuqi Qian ◽  
Aigen Fu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Gene Families ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Range Of Functions ◽  
Eukaryotic Organisms

The basic helix-loop-helix (bHLH) transcription factor family is one of the largest transcription factor gene families in Arabidopsis thaliana, and contains a bHLH motif that is highly conserved throughout eukaryotic organisms. Members of this family have two conserved motifs, a basic DNA binding region and a helix-loop-helix (HLH) region. These proteins containing bHLH domain usually act as homo- or heterodimers to regulate the expression of their target genes, which are involved in many physiological processes and have a broad range of functions in biosynthesis, metabolism and transduction of plant hormones. Although there are a number of articles on different aspects to provide detailed information on this family in plants, an overall summary is not available. In this review, we summarize various aspects of related studies that provide an overview of insights into the pleiotropic regulatory roles of these transcription factors in plant growth and development, stress response, biochemical functions and the web of signaling networks. We then provide an overview of the functional profile of the bHLH family and the regulatory mechanisms of other proteins.

T-cell acute lymphoblastic leukemia--the associated gene SCL/tal codes for a 42-Kd nuclear phosphoprotein

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2858-2866 ◽  
Author(s):  
AN Goldfarb ◽  
S Goueli ◽  
D Mickelson ◽  
JM Greenberg
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Nuclear Localization ◽  
Dna Sequences ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Bhlh Protein ◽  
Helix Loop Helix ◽  
Cell Acute Lymphoblastic Leukemia

SCL/tal is a putative oncogene originally identified through its involvement in the translocation t(1;14)(p32;q11) present in the leukemic cell line DU.528. Subsequent studies have shown an upstream deletion activating expression of SCL/tal to be one of the most common genetic lesions in T-cell acute lymphoblastic leukemia (T-ALL). The cDNA sequence of SCL/tal encodes a basic helix-loop-helix (bHLH) protein with regions of marked homology to lyl-1 and tal-2, two other bHLH proteins involved in T-ALL chromosomal translocations. The bHLH motif suggests that the SCL/tal product localizes to the nucleus, binds to specific DNA sequences, and regulates transcription of a specific array of target genes. Our studies directly identify the SCL/tal product as a 42-Kd phosphoprotein that efficiently localizes to the nucleus. Deletion mutagenesis has allowed identification of a region critical for nuclear localization, a region that corresponds to the DNA- binding basic domain within the bHLH motif. Because this domain is shared by lyl-1 and tal-2, these latter putative T-cell oncoproteins probably use a nuclear localization mechanism identical to that of SCL/tal.

Dual role of the basic helix-loop-helix transcription factor scleraxis in mesoderm formation and chondrogenesis during mouse embryogenesis

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4317-4329 ◽  
Author(s):  
D. Brown ◽  
D. Wagner ◽  
X. Li ◽  
J.A. Richardson ◽  
E.N. Olson
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Embryonic Stem ◽  
Primitive Streak ◽  
Axial Skeleton ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Mesoderm Formation ◽  
Cell Layers

Scleraxis is a basic helix-loop-helix (bHLH) transcription factor shown previously to be expressed in developing chondrogenic cell lineages during embryogenesis. To investigate its function in embryonic development, we produced scleraxis-null mice by gene targeting. Homozygous mutant embryos developed normally until the early egg cylinder stage (embryonic day 6.0), when they became growth-arrested and failed to gastrulate. Consistent with this early embryonic phenotype, scleraxis was found to be expressed throughout the embryo at the time of gastrulation before becoming restricted to chondrogenic precursor cells at embryonic day 9.5. At the time of developmental arrest, scleraxis-null embryos consisted of ectodermal and primitive endodermal cell layers, but lacked a primitive streak or recognizable mesoderm. Analysis of molecular markers of the three embryonic germ layers confirmed that scleraxis mutant embryos were unable to form mesoderm. By generating chimeric embryos, using lacZ-marked scleraxis-null and wild-type embryonic stem cells, we examined the ability of mutant cells to contribute to regions of the embryo beyond the time of lethality of homozygous mutants. Scleraxis-null cells were specifically excluded from the sclerotomal compartment of somites, which gives rise to the axial skeleton, and from developing ribs, but were able to contribute to most other regions of the embryo, including mesoderm-derived tissues. These results reveal an essential early role for scleraxis in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages, and suggest that scleraxis target genes mediate these processes.

scholarly journals Notch Signaling Induces Rapid Degradation of Achaete-Scute Homolog 1

2002 ◽  
Vol 22 (9) ◽  
pp. 3129-3139 ◽  
Author(s):  
Virote Sriuranpong ◽  
Michael W. Borges ◽  
Christopher L. Strock ◽  
Eric K. Nakakura ◽  
D. Neil Watkins ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Neural Development ◽  
Transcriptional Repression ◽  
Bhlh Protein ◽  
Bhlh Transcription Factor ◽  
Small Cell Lung ◽  
Rapid Degradation ◽  
Helix Loop Helix ◽  
Initial Appearance ◽  
Enhancer Of Split

ABSTRACT In neural development, Notch signaling plays a key role in restricting neuronal differentiation, promoting the maintenance of progenitor cells. Classically, Notch signaling causes transactivation of Hairy-enhancer of Split (HES) genes which leads to transcriptional repression of neural determination and differentiation genes. We now report that in addition to its known transcriptional mechanism, Notch signaling also leads to rapid degradation of the basic helix-loop-helix (bHLH) transcription factor human achaete-scute homolog 1 (hASH1). Using recombinant adenoviruses expressing active Notch1 in small-cell lung cancer cells, we showed that the initial appearance of Notch1 coincided with the loss of hASH1 protein, preceding the full decay of hASH1 mRNA. Overexpression of HES1 alone was capable of down-regulating hASH1 mRNA but could not replicate the acute reduction of hASH1 protein induced by Notch1. When adenoviral hASH1 was coinfected with Notch1, we still observed a dramatic and abrupt loss of the exogenous hASH1 protein, despite high levels of ongoing hASH1 RNA expression. Notch1 treatment decreased the apparent half-life of the adenoviral hASH1 protein and increased the fraction of hASH1 which was polyubiquitinylated. The proteasome inhibitor MG132 reversed the Notch1-induced degradation. The Notch RAM domain was dispensable but a lack of the OPA and PEST domains inactivated this Notch1 action. Overexpression of the hASH1-dimerizing partner E12 could protect hASH1 from degradation. This novel function of activated Notch to rapidly degrade a class II bHLH protein may prove to be important in many contexts in development and in cancer.

scholarly journals SmbHLH37 functions antagonistically with SmMYC2 in regulating jasmonate-mediated biosynthesis of phenolic acids in Salvia miltiorrhiza

2018 ◽  
Author(s):  
Tang-Zhi Du ◽  
Jun-Feng Niu ◽  
Jiao Su ◽  
Sha-Sha Li ◽  
Xiao-Rong Guo ◽  
...  
Keyword(s):  
Target Genes ◽  
Salvia Miltiorrhiza ◽  
Functional Characterization ◽  
Constitutive Expression ◽  
Defense Responses ◽  
Bhlh Transcription Factor ◽  
Bhlh Gene ◽  
Helix Loop Helix ◽  
Jaz Proteins ◽  
Ja Signaling

AbstractJasmonates (JAs) are integral to various defense responses and induce biosynthesis of many secondary metabolites. MYC2, a basic helix-loop-helix (bHLH) transcription factor (TF), acts as a transcriptional activator of JA signaling. MYC2 is repressed by the JASMONATE ZIM-domain (JAZ) proteins in the absence of JA, but de-repressed by the protein complex SCFCOI1 on perception of JA. We previously reported that overexpression of SmMYC2 promotes the production of salvianolic acid B (Sal B) in Salvia miltiorrhiza. However, the responsible molecular mechanism is unclear. Here, we showed that SmMYC2 binds to and activates the promoters of its target genes SmTAT1, SmPAL1, and SmCYP98A14 to activate Sal B accumulations. SmbHLH37, a novel bHLH gene significantly up-regulated by constitutive expression of SmMYC2, was isolated from S. miltiorrhiza for detailed functional characterization. SmbHLH37 forms a homodimer and interacts with SmJAZ3/8. Overexpression of SmbHLH37 substantially decreased yields of Sal B. SmbHLH37 binds to the promoters of its target genes SmTAT1 and SmPAL1 and blocks their expression to suppress the pathway for Sal B biosynthesis. These results indicate that SmbHLH37 negatively regulates JA signaling and functions antagonistically with SmMYC2 in regulating Sal B biosynthesis in S. miltiorrhiza.

Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains

2002 ◽  
Vol 361 (3) ◽  
pp. 641-651 ◽  
Author(s):  
Martin KNÖFLER ◽  
Gudrun MEINHARDT ◽  
Sandra BAUER ◽  
Thomas LOREGGER ◽  
Richard VASICEK ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Transcriptional Repressor ◽  
Bhlh Protein ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Class A ◽  
Helix Loop Helix ◽  
Bhlh Factors ◽  
E Boxes

The basic helix-loop-helix (bHLH) transcription factor, Hand1, plays an important role in the development of the murine extra-embryonic trophoblast cell lineage. In the present study, we have analysed the expression of Hand1 in human extra-embryonic cell types and determined its binding specificity and transcriptional activity upon interaction with different class A bHLH factors. Northern blotting and in situ hybridization showed that Hand1 mRNA is specifically expressed in amnion cells at different stages of gestation. Accordingly, we demonstrate that the protein is exclusively produced in the amniotic epithelium in vivo and in purified amnion cells in vitro using a novel polyclonal Hand1 antiserum. Reverse transcriptase-PCR and immunohistochemical staining of blastocysts revealed the production of Hand1 mRNA and polypeptide in the trophectodermal cell layer. In the presence of E12/E47, Hand1 stimulated the transcription of luciferase reporters harbouring degenerate E-boxes, suggesting that E-proteins are potential dimerization partners in trophoblastic tumour and amnion cells. In contrast, Hand1 diminished E12/E47-dependent transcription of reporters containing perfect E-boxes by inhibiting the interaction of Hand1/E-protein heterodimers with the palindromic cognate sequence. Furthermore, we show that Hand1 down-regulated GAL—E12-dependent reporter expression, indicating that the protein can also act directly as a transcriptional repressor. Mutational analyses of GAL-Hand1 suggested that two protein regions located within its N-terminal portion mainly confer the repressing activity. In conclusion, human Hand1 may play an important role in the differentiation of the amniotic membrane and the pre-implanting trophoblast. Furthermore, the data suggest that Hand1 can act as a repressor by two independent mechanisms; sequestration of class A bHLH factors from E-boxes and inhibition of their transcriptional activity.

scholarly journals ZmIBH1-1 regulates plant architecture in maize

2020 ◽  
Vol 71 (10) ◽  
pp. 2943-2955 ◽  
Author(s):  
Yingying Cao ◽  
Haixia Zeng ◽  
Lixia Ku ◽  
Zhenzhen Ren ◽  
Yun Han ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plant Architecture ◽  
Target Genes ◽  
Affinity Purification ◽  
Negative Regulator ◽  
Planting Density ◽  
Leaf Angle ◽  
Bhlh Transcription Factor ◽  
Helix Loop Helix ◽  
Regulatory Model

Abstract Leaf angle (LA) is a critical agronomic trait in maize, with more upright leaves allowing higher planting density, leading to more efficient light capture and higher yields. A few genes responsible for variation in LA have been identified by map-based cloning. In this study, we cloned maize ZmIBH1-1, which encodes a bHLH transcription factor with both a basic binding region and a helix-loop-helix domain, and the results of qRT-PCR showed that it is a negative regulator of LA. Histological analysis indicated that changes in LA were mainly caused by differential cell wall lignification and cell elongation in the ligular region. To determine the regulatory framework of ZmIBH1-1, we conducted RNA-seq and DNA affinity purification (DAP)-seq analyses. The combined results revealed 59 ZmIBH1-1-modulated target genes with annotations, and they were mainly related to the cell wall, cell development, and hormones. Based on the data, we propose a regulatory model for the control of plant architecture by ZmIBH1-1 in maize.

scholarly journals T-cell acute lymphoblastic leukemia--the associated gene SCL/tal codes for a 42-Kd nuclear phosphoprotein

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2858-2866 ◽  
Author(s):  
AN Goldfarb ◽  
S Goueli ◽  
D Mickelson ◽  
JM Greenberg
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Nuclear Localization ◽  
Dna Sequences ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Bhlh Protein ◽  
Helix Loop Helix ◽  
Cell Acute Lymphoblastic Leukemia

Abstract SCL/tal is a putative oncogene originally identified through its involvement in the translocation t(1;14)(p32;q11) present in the leukemic cell line DU.528. Subsequent studies have shown an upstream deletion activating expression of SCL/tal to be one of the most common genetic lesions in T-cell acute lymphoblastic leukemia (T-ALL). The cDNA sequence of SCL/tal encodes a basic helix-loop-helix (bHLH) protein with regions of marked homology to lyl-1 and tal-2, two other bHLH proteins involved in T-ALL chromosomal translocations. The bHLH motif suggests that the SCL/tal product localizes to the nucleus, binds to specific DNA sequences, and regulates transcription of a specific array of target genes. Our studies directly identify the SCL/tal product as a 42-Kd phosphoprotein that efficiently localizes to the nucleus. Deletion mutagenesis has allowed identification of a region critical for nuclear localization, a region that corresponds to the DNA- binding basic domain within the bHLH motif. Because this domain is shared by lyl-1 and tal-2, these latter putative T-cell oncoproteins probably use a nuclear localization mechanism identical to that of SCL/tal.

Identification of TAL1/SCL Target Genes through siRNA and Microarray Expression Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4294-4294
Author(s):  
Jennifer O’Neil ◽  
Adolfo A. Ferrando ◽  
Teresa Palomero ◽  
A. Thomas Look
Keyword(s):  
Expression Analysis ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Jurkat Cells ◽  
Phenotypic Characterization ◽  
Bhlh Protein ◽  
Helix Loop Helix ◽  
Microarray Expression Analysis ◽  
Clonal Cell Lines ◽  
Microarray Expression

Abstract TAL1 is a basic helix-loop-helix (bHLH) protein that is essential for hematopoiesis. Activation of the TAL1/SCL gene occurs in as many as 60% of patients with pediatric and adult T cell acute lymphoblastic leukemia (T-ALL). Mouse models have demonstrated that TAL1 transforms by inhibiting the function of E proteins, however the transcriptional targets of TAL1 that contribute to leukemia are not known. In this study we sought to identify targets of TAL1 that contribute to the transformation of thymocytes through siRNA-mediated knockdown of TAL1 expression in the Jurkat T-ALL cell line that expresses high levels of TAL1. We have generated several clonal cell lines that stably express a siRNA directed against TAL1 with up to 90% knockdown of TAL1 at both the RNA and protein level. Phenotypic characterization of these cells revealed that Jurkat cells with decreased TAL1 expression display a decreased proliferative capacity. This phenotype is augmented in lower serum concentrations in which wild-type and siRNA control Jurkat cells proliferate rapidly. Microarray expression analysis using Affymetrix U133 Plus 2.0 arrays has revealed that TAL1 is a global regulator of gene expression and that many pathways are affected by TAL1 knockdown, including those implicated in cell growth and proliferation. This data will enable us to dissect the downstream pathways of TAL1 by knocking-down or overexpressing these TAL1 targets (depending on whether they are up- or down-regulated in the absence of TAL1), and assessing whether they affect the proliferative rate or survival T-ALL cells. We anticipate that we will identify and validate potential therapeutic targets for TAL1-induced leukemia using this combination of approaches.

scholarly journals Calcium Regulation of Myogenesis by Differential Calmodulin Inhibition of Basic Helix-Loop-Helix Transcription Factors

2008 ◽  
Vol 19 (6) ◽  
pp. 2509-2519 ◽  
Author(s):  
Jannek Hauser ◽  
Juha Saarikettu ◽  
Thomas Grundström
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Myogenic Differentiation ◽  
Bhlh Protein ◽  
Channel Blockers ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Protein ◽  
Bhlh Transcription Factors

The members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors are critical regulators of skeletal muscle differentiation that function as heterodimers with ubiquitously expressed E-protein bHLH transcription factors. These heterodimers must compete successfully with homodimers of E12 and other E-proteins to enable myogenesis. Here, we show that E12 mutants resistant to Ca2+-loaded calmodulin (CaM) inhibit MyoD-initiated myogenic conversion of transfected fibroblasts. Ca2+ channel blockers reduce, and Ca2+ stimulation increases, transcription by coexpressed MyoD and wild-type E12 but not CaM-resistant mutant E12. Furthermore, CaM-resistant E12 gives lower MyoD binding and higher E12 binding to a MyoD-responsive promoter in vivo and cannot rescue myogenic differentiation that has been inhibited by siRNA against E12 and E47. Our data support the concept that Ca2+-loaded CaM enables myogenesis by inhibiting DNA binding of E-protein homodimers, thereby promoting occupancy of myogenic bHLH protein/E-protein heterodimers on promoters of myogenic target genes.

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