Functional Roles of Basic Helix-Loop-Helix (bHLH) Transcription Factors in Proliferation and Differentiation of Neural Tube Cells

Spina Bifida ◽  
1999 ◽  
pp. 256-264
Author(s):  
Kikuo Suda ◽  
Masakazu Miyajima ◽  
Hajime Arai ◽  
Kiyoshi Sato
2000 ◽  
Vol 20 (13) ◽  
pp. 4826-4837 ◽  
Author(s):  
Gino Poulin ◽  
Mélanie Lebel ◽  
Michel Chamberland ◽  
Francois W. Paradis ◽  
Jacques Drouin

ABSTRACT Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression of NeuroD1 in pituitary corticotroph cells and a direct physical interaction between bHLH heterodimers and Pitx1 that results in transcriptional synergism. The interaction between the bHLH and homeodomains is restricted to ubiquitous (class A) bHLH and to the Pitx subfamily. Since bHLH heterodimers interact with Pitx factors through their ubiquitous moiety, this mechanism may be implicated in other developmental processes involving bHLH factors, such as neurogenesis and myogenesis.


2020 ◽  
Author(s):  
Gwen Swinnen ◽  
Margaux De Meyer ◽  
Jacob Pollier ◽  
Francisco Javier Molina-Hidalgo ◽  
Evi Ceulemans ◽  
...  

ABSTRACTSpecialized metabolites are produced by plants to fend off biotic enemies. Across the plant kingdom, the biosynthesis of these defense compounds is promoted by jasmonate signaling in which clade IIIe basic helix-loop-helix (bHLH) transcription factors take on a central role. Tomato (Solanum lycopersicum) produces cholesterol-derived steroidal glycoalkaloids (SGAs) that act as phytoanticipins against a broad variety of herbivores and pathogens. The biosynthesis of SGAs from cholesterol occurs constitutively in tomato plants and can be further stimulated by jasmonates. Here, we demonstrate that the two tomato clade IIIe bHLH transcription factors, MYC1 and MYC2, redundantly and specifically control the constitutive biosynthesis of SGAs. Double myc1 myc2 loss-of-function tomato hairy roots displayed suppressed constitutive expression of cholesterol and SGA biosynthesis genes, and consequently severely reduced levels of the main tomato SGAs α-tomatine and dehydrotomatine. In contrast, basal expression of genes involved in canonical jasmonate signaling or in the biosynthesis of highly jasmonate-inducible phenylpropanoid-polyamine conjugates was not affected. Furthermore, CRISPR-Cas9(VQR)-mediated genome editing of a specific cis-regulatory element, targeted by MYC1/2, in the promoter of a cholesterol biosynthesis gene led to decreased constitutive expression of this gene, but did not affect its jasmonate inducibility. Our results demonstrate that clade IIIe bHLH transcriptional regulators might have evolved to regulate the biosynthesis of specific constitutively accumulating specialized metabolites independent of jasmonate signaling.One sentence summaryThe clade IIIe basic helix-loop-helix transcription factors MYC1 and MYC2 control the constitutive biosynthesis of tomato steroidal glycoalkaloids and might do so independently of jasmonate signaling.


2007 ◽  
Vol 6 (4) ◽  
pp. 734-743 ◽  
Author(s):  
Setsu Endoh-Yamagami ◽  
Kiyoshi Hirakawa ◽  
Daisuke Morioka ◽  
Ryouichi Fukuda ◽  
Akinori Ohta

ABSTRACT The expression of the ALK1 gene, which encodes cytochrome P450, catalyzing the first step of alkane oxidation in the alkane-assimilating yeast Yarrowia lipolytica, is highly regulated and can be induced by alkanes. Previously, we identified a cis-acting element (alkane-responsive element 1 [ARE1]) in the ALK1 promoter. We showed that a basic helix-loop-helix (bHLH) protein, Yas1p, binds to ARE1 in vivo and mediates alkane-dependent transcription induction. Yas1p, however, does not bind to ARE1 by itself in vitro, suggesting that Yas1p requires another bHLH protein partner for its DNA binding, as many bHLH transcription factors function by forming heterodimers. To identify such a binding partner of Yas1p, here we screened open reading frames encoding proteins with the bHLH motif from the Y. lipolytica genome database and identified the YAS2 gene. The deletion of the YAS2 gene abolished the alkane-responsive induction of ALK1 transcription and the growth of the yeast on alkanes. We revealed that Yas2p has transactivation activity. Furthermore, Yas1p and Yas2p formed a protein complex that was required for the binding of these proteins to ARE1. These findings allow us to postulate a model in which bHLH transcription factors Yas1p and Yas2p form a heterocomplex and mediate the transcription induction in response to alkanes.


2021 ◽  
Author(s):  
Daniela M. Lichtblau ◽  
Birte Schwarz ◽  
Dibin Baby ◽  
Christopher Endres ◽  
Christin Sieberg ◽  
...  

Plants use the micronutrient iron (Fe) efficiently to balance the requirements for Fe during growth with its potential cytotoxic effects. A cascade of basic helix-loop-helix (bHLH) transcription factors is initiated by bHLH proteins of the subgroups IVb and IVc. This induces more than 50 genes in higher plants that can be grouped in co-expression clusters. Gene co-expression networks contain information on functional protein interactomes. We conducted a targeted yeast two-hybrid screen with pairwise combinations of 23 proteins stemming from previously characterized Fe-deficiency-induced gene co-expression clusters and regulators. We identified novel and described interactions, as well as interaction hubs with multiple interactions within the network. We found that BRUTUS-LIKE E3 ligases (BTSL1, BTSL2) interacted with basic helix-loop-helix (bHLH) transcription factors of the subgroups IVb and IVc including PYE, bHLH104 and ILR3, and with small FE UPTAKE-INDUCING PEPTIDE3/IRON MAN1 (FEP3/IMA1). Through deletion studies and with support of molecular docking, we mapped the interaction sites to three-amino-acid regions in BTSL1 and FEP3/IMA1. The FEP3/IMA1 active residues are present in interacting sites of the bHLH IVc factors. FEP3/IMA1 attenuated interaction of BTSL1 with bHLH proteins in a quantitative yeast three-hybrid assay suggesting that it is an inhibitor. Co-expression of BTSL1 and bHLH IVb and IVc factors uncovered unexpected patterns of subcellular localization. Combining deletion mapping, protein interaction and physiological analysis, we discuss the model that FEP3/IMA1 is a small effector protein inhibiting BTSL1/BTSL2-mediated degradation of bHLH subgroup IVb and IVc proteins.


2008 ◽  
Vol 19 (6) ◽  
pp. 2509-2519 ◽  
Author(s):  
Jannek Hauser ◽  
Juha Saarikettu ◽  
Thomas Grundström

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Karen A. Hudson ◽  
Matthew E. Hudson

The complete genome sequence of soybean allows an unprecedented opportunity for the discovery of the genes controlling important traits. In particular, the potential functions of regulatory genes are a priority for analysis. The basic helix-loop-helix (bHLH) family of transcription factors is known to be involved in controlling a wide range of systems critical for crop adaptation and quality, including photosynthesis, light signalling, pigment biosynthesis, and seed pod development. Using a hidden Markov model search algorithm, 319 genes with basic helix-loop-helix transcription factor domains were identified within the soybean genome sequence. These were classified with respect to their predicted DNA binding potential, intron/exon structure, and the phylogeny of the bHLH domain. Evidence is presented that the vast majority (281) of these 319 soybean bHLH genes are expressed at the mRNA level. Of these soybean bHLH genes, 67% were found to exist in two or more homeologous copies. This dataset provides a framework for future studies on bHLH gene function in soybean. The challenge for future research remains to define functions for the bHLH factors encoded in the soybean genome, which may allow greater flexibility for genetic selection of growth and environmental adaptation in this widely grown crop.


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