scholarly journals Atoh8 in Development and Disease

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Satya Srirama Karthik Divvela ◽  
Darius Saberi ◽  
Beate Brand-Saberi
Keyword(s):  
Transcription Factors ◽  
Embryonic Development ◽  
Subcellular Location ◽  
Transcriptional Regulators ◽  
Special Group ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Disease Initiation ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins

Atoh8 belongs to a large superfamily of transcriptional regulators called basic helix-loop-helix (bHLH) proteins. bHLH proteins have been identified in a wide range of organisms from yeast to humans. The members of this special group of transcription factors were found to be involved not only in embryonic development but also in disease initiation and its progression. Given their importance in several fundamental processes, the translation, subcellular location and turnover of bHLH proteins is tightly regulated. Alterations in the expression of bHLH proteins have been associated with multiple diseases also in context with Atoh8 which seems to unfold its functions as both transcriptional activator and repressor. Like many other bHLH transcription factors, so far, Atoh8 has also been observed to be involved in both embryonic development and carcinogenesis where it mainly acts as tumor suppressor. This review summarizes our current understanding of Atoh8 structure, function and regulation and its complex and partially controversial involvement in development and disease.

scholarly journals Genetic Manipulation of Transcriptional Regulators Alters Nicotine Biosynthesis in Tobacco

2020 ◽  
Vol 61 (6) ◽  
pp. 1041-1053 ◽  
Author(s):  
Shunya Hayashi ◽  
Mutsumi Watanabe ◽  
Makoto Kobayashi ◽  
Takayuki Tohge ◽  
Takashi Hashimoto ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Genetic Manipulation ◽  
Transcriptional Regulators ◽  
Knockout Mutant ◽  
Gene Encoding ◽  
Helix Loop Helix ◽  
Wide Range ◽  
Nicotine Biosynthesis ◽  
Transient Overexpression ◽  
The Impact

Abstract The toxic alkaloid nicotine is produced in the roots of Nicotiana species and primarily accumulates in leaves as a specialized metabolite. A series of metabolic and transport genes involved in the nicotine pathway are coordinately upregulated by a pair of jasmonate-responsive AP2/ERF-family transcription factors, NtERF189 and NtERF199, in the roots of Nicotiana tabacum (tobacco). In this study, we explored the potential of manipulating the expression of these transcriptional regulators to alter nicotine biosynthesis in tobacco. The transient overexpression of NtERF189 led to alkaloid production in the leaves of Nicotiana benthamiana and Nicotiana alata. This ectopic production was further enhanced by co-overexpressing a gene encoding a basic helix-loop-helix-family MYC2 transcription factor. Constitutive and leaf-specific overexpression of NtERF189 increased the accumulation of foliar alkaloids in transgenic tobacco plants but negatively affected plant growth. By contrast, in a knockout mutant of NtERF189 and NtERF199 obtained through CRISPR/Cas9-based genome editing, alkaloid levels were drastically reduced without causing major growth defects. Metabolite profiling revealed the impact of manipulating the nicotine pathway on a wide range of nitrogen- and carbon-containing metabolites. Our findings provide insights into the biotechnological applications of engineering metabolic pathways by targeting transcription factors.

scholarly journals The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors

2019 ◽  
Vol 20 (21) ◽  
pp. 5306 ◽  
Author(s):  
Aneta Tarczewska ◽  
Beata Greb-Markiewicz
Keyword(s):  
Transcription Factors ◽  
Phase Separation ◽  
Transcription Regulation ◽  
Experimental Studies ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins ◽  
Disordered Regions

The bHLH proteins are a family of eukaryotic transcription factors regulating expression of a wide range of genes involved in cell differentiation and development. They contain the Helix-Loop-Helix (HLH) domain, preceded by a stretch of basic residues, which are responsible for dimerization and binding to E-box sequences. In addition to the well-preserved DNA-binding bHLH domain, these proteins may contain various additional domains determining the specificity of performed transcriptional regulation. According to this, the family has been divided into distinct classes. Our aim was to emphasize the significance of existing disordered regions within the bHLH transcription factors for their functionality. Flexible, intrinsically disordered regions containing various motives and specific sequences allow for multiple interactions with transcription co-regulators. Also, based on in silico analysis and previous studies, we hypothesize that the bHLH proteins have a general ability to undergo spontaneous phase separation, forming or participating into liquid condensates which constitute functional centers involved in transcription regulation. We shortly introduce recent findings on the crucial role of the thermodynamically liquid-liquid driven phase separation in transcription regulation by disordered regions of regulatory proteins. We believe that further experimental studies should be performed in this field for better understanding of the mechanism of gene expression regulation (among others regarding oncogenes) by important and linked to many diseases the bHLH transcription factors.

scholarly journals The effector FEP3/IRON MAN1 modulates interaction between BRUTUS-LIKE1 and bHLH subgroup IVb and IVc proteins

2021 ◽  
Author(s):  
Daniela M. Lichtblau ◽  
Birte Schwarz ◽  
Dibin Baby ◽  
Christopher Endres ◽  
Christin Sieberg ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Higher Plants ◽  
Deletion Mapping ◽  
Functional Protein ◽  
E3 Ligases ◽  
Interaction Sites ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins

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.

scholarly journals Insights into the Diversification of Subclade IVa bHLH Transcription Factors in Fabaceae

2020 ◽  
Author(s):  
Hayato Suzuki ◽  
Hikaru Seki ◽  
Toshiya Muranaka
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Lotus Japonicus ◽  
Helix Loop Helix ◽  
Saponin Biosynthesis ◽  
Plant Families ◽  
Almost All ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins ◽  
Group 1

Abstract Background: Fabaceae plants appear to contain larger numbers of subclade IVa basic-helix-loop-helix (bHLH) transcription factors than other plant families, and some members of this subclade have been identified as saponin biosynthesis regulators. We aimed to systematically elucidate the diversification of this subclade and obtain insights into the evolutionary history of saponin biosynthesis regulation in Fabaceae.Results: In this study, we collected sequences of subclade IVa bHLH proteins from 40 species, including fabids and other plants, and found greater numbers of subclade IVa bHLHs in Fabaceae. We confirmed conservation of the bHLH domain, C-terminal ACT-like domain, and exon-intron organisation among almost all subclade IVa members in model legumes, supporting the results of our classification. Phylogenetic tree-based classification of subclade IVa revealed the presence of three different groups. Interestingly, most Fabaceae subclade IVa bHLHs fell into group 1, which contained all legume saponin biosynthesis regulators identified to date. These observations support the co-occurrence and Fabaceae-specific diversification of saponin biosynthesis regulators. Comparing the expression of orthologous genes in Glycine max, Medicago truncatula, and Lotus japonicus, orthologues of MtTSAR1 (the first identified soyasaponin biosynthesis regulatory transcription factor) were not expressed in the same tissues, suggesting that group 1 members have gained different expression patterns and contributions to saponin biosynthesis during their duplication and divergence. On the other hand, groups 2 and 3 possessed fewer members, and their phylogenetic relationships and expression patterns were highly conserved, indicating that their activities may be conserved across Fabaceae.Conclusions: This study suggests subdivision and diversification of subclade IVa bHLHs in Fabaceae plants. The results will be useful for candidate selection of unidentified saponin biosynthesis regulators. Furthermore, the functions of groups 2 and 3 members are interesting targets for clarifying the evolution of subclade IVa bHLH transcription factors in Fabaceae.

scholarly journals Genome-wide analysis of basic helix-loop-helix (bHLH) transcription factors in papaya (Carica papaya L.)

2019 ◽  
Author(s):  
Min Yang ◽  
Hu Yang ◽  
Ruibin Kuang ◽  
Chenping Zhou ◽  
Bingxiong Huang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Abiotic Stress ◽  
Carica Papaya ◽  
Genome Wide Analysis ◽  
Cis Element ◽  
Helix Loop Helix ◽  
Genome Wide ◽  
Gene Structures ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins

Abstract Background : As a superfamily of transcription factors (TFs), the basic helix-loop-helix (bHLH) proteins have been identified and functionally characterized in many plants. However, no comprehensive analysis of the bHLH family in papaya ( Carica papaya L. ) has been reported previously. Results: In this study, a total of 73 CpbHLH genes were found in papaya, and these genes were classified into 18 subfamilies based on phylogenetic analysis, with one orphans. Almost all of the CpbHLH in the same subfamily shared similar gene structures and protein motifs according to an analysis of exon/intron organizations and motif compositions. The number of exons in CpbHLH genes varied from 1 to 11 with an average of 5. The amino acid sequences of the bHLH domains were quite conservative, especially Leu-27 and Leu-63. Promoter cis -element analysis revealed that most of the CpbHLH genes contained cis -elements that can respond to various biotic/abiotic stress-related events. Gene ontology (GO) analysis revealed that Cp bHLH mainly functions in protein dimerization activity and DNA-binding, and most Cp bHLH proteins were predicted to localize in the nucleus. Abiotic stress treatment and quantitative real-time PCR (qRT-PCR) revealed some predicted CpbHLH genes that might be responsible for abiotic stress responses in papaya. Conclusions : A total of 73 bHLH transcription factors were identified from papaya, and their gene structures, conserved domains, sequence features, phylogenetic relationship, promoter cis -element, GO annotation and gene expression profiles responsible for abiotic stress were investigated. Our findings lay a foundation for further evolutionary and functional elucidation of Cp bHLHs. Keywords : papaya, genome-wide analysis, bHLH transcription factors, abiotic stress

scholarly journals Insights into the diversification of subclade IVa bHLH transcription factors in Fabaceae

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hayato Suzuki ◽  
Hikaru Seki ◽  
Toshiya Muranaka
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
Lotus Japonicus ◽  
Helix Loop Helix ◽  
Saponin Biosynthesis ◽  
Plant Families ◽  
Almost All ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins ◽  
Group 1

Abstract Background Fabaceae plants appear to contain larger numbers of subclade IVa basic-helix-loop-helix (bHLH) transcription factors than other plant families, and some members of this subclade have been identified as saponin biosynthesis regulators. We aimed to systematically elucidate the diversification of this subclade and obtain insights into the evolutionary history of saponin biosynthesis regulation in Fabaceae. Results In this study, we collected sequences of subclade IVa bHLH proteins from 40 species, including fabids and other plants, and found greater numbers of subclade IVa bHLHs in Fabaceae. We confirmed conservation of the bHLH domain, C-terminal ACT-like domain, and exon-intron organisation among almost all subclade IVa members in model legumes, supporting the results of our classification. Phylogenetic tree-based classification of subclade IVa revealed the presence of three different groups. Interestingly, most Fabaceae subclade IVa bHLHs fell into group 1, which contained all legume saponin biosynthesis regulators identified to date. These observations support the co-occurrence and Fabaceae-specific diversification of saponin biosynthesis regulators. Comparing the expression of orthologous genes in Glycine max, Medicago truncatula, and Lotus japonicus, orthologues of MtTSAR1 (the first identified soyasaponin biosynthesis regulatory transcription factor) were not expressed in the same tissues, suggesting that group 1 members have gained different expression patterns and contributions to saponin biosynthesis during their duplication and divergence. On the other hand, groups 2 and 3 possessed fewer members, and their phylogenetic relationships and expression patterns were highly conserved, indicating that their activities may be conserved across Fabaceae. Conclusions This study suggests subdivision and diversification of subclade IVa bHLHs in Fabaceae plants. The results will be useful for candidate selection of unidentified saponin biosynthesis regulators. Furthermore, the functions of groups 2 and 3 members are interesting targets for clarifying the evolution of subclade IVa bHLH transcription factors in Fabaceae.

scholarly journals A Classification of Basic Helix-Loop-Helix Transcription Factors of Soybean

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Karen A. Hudson ◽  
Matthew E. Hudson
Keyword(s):  
Transcription Factors ◽  
Genome Sequence ◽  
Search Algorithm ◽  
Soybean Genome ◽  
Binding Potential ◽  
Future Research ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Wide Range

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.

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.

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