scholarly journals The initiation of Otx2 expression in the developing mouse retina requires a unique enhancer and either Ascl1 or Neurog2 activity

Development ◽  
2021 ◽  
Author(s):  
Michael L. Kaufman ◽  
Noah B. Goodson ◽  
Ko Uoon Park ◽  
Michael Schwanke ◽  
Emma Office ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Cell Formation ◽  
Mouse Retina ◽  
Bhlh Transcription Factor ◽  
Enhancer Element ◽  
Retinal Progenitor ◽  
Helix Loop Helix ◽  
Bhlh Factors ◽  
Simultaneous Loss

During retinal development, a large subset of progenitors upregulates the transcription factor Otx2, which is required for photoreceptor and bipolar cell formation. How these retinal progenitor cells initially activate Otx2 expression is unclear. To address this, we investigated the cis-regulatory network that controls Otx2 expression. We identified a minimal enhancer element, DHS-4D, that drove expression in newly formed OTX2+ cells. CRISPR/Cas9 mediated deletion of DHS-4D reduced OTX2 expression, but this effect was diminished in postnatal development. Systematic mutagenesis of the enhancer revealed that three basic helix-loop-helix (bHLH) transcription factor binding sites were required for its activity. Single cell RNA-sequencing of nascent Otx2+ cells identified the bHLH factors Ascl1 and Neurog2 as candidate regulators. CRISPR/Cas9 targeting of these factors showed that only the simultaneous loss of Ascl1 and Neurog2 prevented OTX2 expression. Our findings suggest that Ascl1 and Neurog2 act redundantly or in a compensatory fashion to activate the DHS-4D enhancer and Otx2 expression. We observed redundancy or compensation at both the transcriptional and enhancer utilization levels, suggesting that the mechanisms governing Otx2 regulation in the retina are flexible and robust.

scholarly journals BETA3, a novel helix-loop-helix protein, can act as a negative regulator of BETA2 and MyoD-responsive genes.

1996 ◽  
Vol 16 (2) ◽  
pp. 626-633 ◽  
Author(s):  
M Peyton ◽  
C M Stellrecht ◽  
F J Naya ◽  
H P Huang ◽  
P J Samora ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Negative Regulator ◽  
Bhlh Transcription Factor ◽  
Pcr Cloning ◽  
Specific Expression ◽  
Class A ◽  
Helix Loop Helix ◽  
E Box ◽  
Class B ◽  
Bhlh Factors

Using degenerate PCR cloning we have identified a novel basic helix-loop-helix (bHLH) transcription factor, BETA3, from a hamster insulin tumor (HIT) cell cDNA library. Sequence analysis revealed that this factor belongs to the class B bHLH family and has the highest degree of homology with another bHLH transcription factor recently isolated in our laboratory, BETA2 (neuroD) (J. E. Lee, S. M. Hollenberg, L. Snider, D. L. Turner, N. Lipnick, and H. Weintraub, Science 268:836-844, 1995; F. J. Naya, C. M. M. Stellrecht, and M.-J. Tsai, Genes Dev. 8:1009-1019, 1995). BETA2 is a brain- and pancreatic-islet-specific bHLH transcription factor and is largely responsible for the tissue-specific expression of the insulin gene. BETA3 was found to be tissue restricted, with the highest levels of expression in HIT, lung, kidney, and brain cells. Surprisingly, despite the homology between BETA2 and BETA3 and its intact basic region, BETA3 is unable to bind the insulin E box in bandshift analysis as a homodimer or as a heterodimer with the class A bHLH factors E12, E47, or BETA1. Instead, BETA3 inhibited both the E47 homodimer and the E47/BETA2 heterodimer binding to the insulin E box. In addition, BETA3 greatly repressed the BETA2/E47 induction of the insulin enhancer in HIT cells as well as the MyoD/E47 induction of a muscle-specific E box in the myoblast cell line C2C12. In contrast, expression of BETA3 had no significant effect on the GAL4-VP16 transcriptional activity. Immunoprecipitation analysis demonstrates that the mechanism of repression is via direct protein-protein interaction, presumably by heterodimerization between BETA3 and class A bHLH factors.

scholarly journals The Basic Helix-Loop-Helix Transcription Factor Cph2 Regulates Hyphal Development in CandidaalbicansPartly via Tec1

2001 ◽  
Vol 21 (19) ◽  
pp. 6418-6428 ◽  
Author(s):  
Shelley Lane ◽  
Song Zhou ◽  
Ting Pan ◽  
Qian Dai ◽  
Haoping Liu
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Binding Sites ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Mitogen Activated Protein Kinase ◽  
Northern Analysis ◽  
Hyphal Development ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

ABSTRACT Candida albicans undergoes a morphogenetic switch from budding yeast to hyphal growth form in response to a variety of stimuli and growth conditions. Multiple signaling pathways, including a Cph1-mediated mitogen-activated protein kinase pathway and an Efg1-mediated cyclic AMP/protein kinase A pathway, regulate the transition. Here we report the identification of a basic helix-loop-helix transcription factor of the Myc subfamily (Cph2) by its ability to promote pseudohyphal growth inSaccharomyces cerevisiae. Like sterol response element binding protein 1, Cph2 has a Tyr instead of a conserved Arg in the basic DNA binding region. Cph2 regulates hyphal development in C. albicans, ascph2/cph2 mutant strains show medium-specific impairment in hyphal development and in the induction of hypha-specific genes. However, many hypha-specific genes do not have potential Cph2 binding sites in their upstream regions. Interestingly, upstream sequences of all known hypha-specific genes are found to contain potential binding sites for Tec1, a regulator of hyphal development. Northern analysis shows that TEC1 transcription is highest in the medium in which cph2/cph2 displays a defect in hyphal development, and Cph2 is necessary for this transcriptional induction of TEC1. In vitro gel mobility shift experiments show that Cph2 directly binds to the two sterol regulatory element 1-like elements upstream of TEC1. Furthermore, the ectopic expression of TEC1 suppresses the defect ofcph2/cph2 in hyphal development. Therefore, the function of Cph2 in hyphal transcription is mediated, in part, through Tec1. We further show that this function of Cph2 is independent of the Cph1- and Efg1-mediated pathways.

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.

Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2513-2523 ◽  
Author(s):  
J.C. Cross ◽  
M.L. Flannery ◽  
M.A. Blanar ◽  
E. Steingrimsson ◽  
N.A. Jenkins ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Promoter ◽  
Giant Cells ◽  
Placental Lactogen ◽  
Specific Gene ◽  
Bhlh Transcription Factor ◽  
Trophoblast Cells ◽  
Positive Role ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Trophoblast cells are the first lineage to form in the mammalian conceptus and mediate the process of implantation. We report the cloning of a basic helix-loop-helix (bHLH) transcription factor gene, Hxt, that is expressed in early trophoblast and in differentiated giant cells. A separate gene, Hed, encodes a related protein that is expressed in maternal deciduum surrounding the implantation site. Overexpression of Hxt in mouse blastomeres directed their development into trophoblast cells in blastocysts. In addition, overexpression of Hxt induced the differentiation of rat trophoblast (Rcho-1) stem cells as assayed by changes in cell adhesion and by activation of the placental lactogen-I gene promoter, a trophoblast giant cell-specific gene. In contrast, the negative HLH regulator, Id-1, inhibited Rcho-1 differentiation and placental lactogen-I transcription. These data demonstrate a role for HLH factors in regulating trophoblast development and indicate a positive role for Hxt in promoting the formation of trophoblast giant cells.

scholarly journals FIT, a regulatory hub for iron deficiency and stress signaling in roots, and FIT-dependent and -independent gene signatures

2020 ◽  
Vol 71 (5) ◽  
pp. 1694-1705 ◽  
Author(s):  
Birte Schwarz ◽  
Petra Bauer
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Fe Deficiency ◽  
Bhlh Transcription Factor ◽  
Root Cells ◽  
Gene Signatures ◽  
Helix Loop Helix ◽  
Independent Gene ◽  
Fe Uptake ◽  
Fe Acquisition

Abstract Iron (Fe) is vital for plant growth. Plants balance the beneficial and toxic effects of this micronutrient, and tightly control Fe uptake and allocation. Here, we review the role of the basic helix–loop–helix (bHLH) transcription factor FIT (FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) in Fe acquisition. FIT is not only essential, it is also a central regulatory hub in root cells to steer and adjust the rate of Fe uptake by the root in a changing environment. FIT regulates a subset of root Fe deficiency (–Fe) response genes. Based on a combination of co-expression network and FIT-dependent transcriptome analyses, we defined a set of FIT-dependent and FIT-independent gene expression signatures and co-expression clusters that encode specific functions in Fe regulation and Fe homeostasis. These gene signatures serve as markers to integrate novel regulatory factors and signals into the –Fe response cascade. FIT forms a complex with bHLH subgroup Ib transcription factors. Furthermore, it interacts with key regulators from different signaling pathways that either activate or inhibit FIT function to adjust Fe acquisition to growth and environmental constraints. Co-expression clusters and FIT protein interactions suggest a connection of –Fe with ABA responses and root cell elongation processes that can be explored in future studies.

scholarly journals Tomato bHLH132 Transcription Factor Controls Growth and Defense and Is Activated by Xanthomonas euvesicatoria Effector XopD During Pathogenesis

2019 ◽  
Vol 32 (12) ◽  
pp. 1614-1622 ◽  
Author(s):  
Jung-Gun Kim ◽  
Mary Beth Mudgett
Keyword(s):  
Transcription Factor ◽  
Protease Activity ◽  
Transcriptional Profiling ◽  
Bhlh Transcription Factor ◽  
Transcription Activator ◽  
Tal Effectors ◽  
Sumo Protease ◽  
Tal Effector ◽  
Helix Loop Helix ◽  
Xanthomonas Euvesicatoria

Effector-dependent manipulation of host transcription is a key virulence mechanism used by Xanthomonas species causing bacterial spot disease in tomato and pepper. Transcription activator-like (TAL) effectors employ novel DNA-binding domains to directly activate host transcription, whereas the non-TAL effector XopD uses a small ubiquitin-like modifier (SUMO) protease activity to represses host transcription. The targets of TAL and non-TAL effectors provide insight to the genes governing susceptibility and resistance during Xanthomonas infection. In this study, we investigated the extent to which the X. euvesicatoria non-TAL effector strain Xe85-10 activates tomato transcription to gain new insight to the transcriptional circuits and virulence mechanisms associated with Xanthomonas euvesicatoria pathogenesis. Using transcriptional profiling, we identified a putative basic helix-loop-helix (bHLH) transcription factor, bHLH132, as a pathogen-responsive gene that is moderately induced by microbe-associated molecular patterns and defense hormones and is highly induced by XopD during X. euvesicatoria infection. We also found that activation of bHLH132 transcription requires the XopD SUMO protease activity. Silencing bHLH132 mRNA expression results in stunted tomato plants with enhanced susceptibility to X. euvesicatoria infection. Our work suggests that bHLH132 is required for normal vegetative growth and development as well as resistance to X. euvesicatoria. It also suggests new transcription-based models describing XopD virulence and recognition in tomato.

scholarly journals The Basic-Region Helix-Loop-Helix Transcription Factor DevR Significantly Affects Polysaccharide Metabolism inAspergillus oryzae

2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Miao Zhuang ◽  
Zhi-Min Zhang ◽  
Long Jin ◽  
Bao-Teng Wang ◽  
Yasuji Koyama ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aspergillus Oryzae ◽  
Bhlh Transcription Factor ◽  
Regulation Mechanism ◽  
Starch Metabolism ◽  
Poor Growth ◽  
Content Type ◽  
Helix Loop Helix ◽  
Amylase Production ◽  
Basic Region

ABSTRACTBasic-region helix-loop-helix (bHLH) proteins are a superfamily of transcription factors that are often involved in the control of growth and differentiation. Recently, it was reported that the bHLH transcription factor DevR is involved in both asexual and sexual development inAspergillus nidulansand regulates the conidial melanin production inAspergillus fumigatus. In this study, we identified and characterized anAspergillus oryzaegene that showed high similarity withdevRofA. nidulansandA. fumigatus(AodevR). In the AodevR-disrupted strain, growth was delayed and the number of conidia was decreased on Czapek-Dox (CD) minimal agar plates, but the conidiation was partially recovered by adding 0.6 M KCl. Simultaneously, the overexpression of AodevRwas induced and resulted in extremely poor growth when the carbon source changed from glucose to polysaccharide (dextrin) in the CD agar plate. Scanning electron microscopy (SEM) indicated that the overexpression of AodevRresulted in extremely thin aberrant hyphal morphology. Conversely, the deletion of AodevRresulted in thicker hyphae and in more resistance to Congo red relative to the control strain. Quantitative reverse transcriptase PCR (RT-PCR) further indicated that AoDevR significantly affects chitin and starch metabolism, and importantly, the overexpression of AodevRinhibited the expression of genes related to starch degradation. A yeast one-hybrid assay suggested that the DevR protein possibly interacted with the promoter ofamyR, which encodes a transcription factor involved in amylase production. Importantly, AoDevR is involved in polysaccharide metabolism and affects the growth of theA. oryzaestrain.IMPORTANCEAspergillus oryzaeis an industrially important filamentous fungus; therefore, a clear understanding of its polysaccharide metabolism and utilization is very important for its industrial utilization. In this study, we revealed that the basic-region helix-loop-helix (bHLH) transcription factor AoDevR is importantly involved in chitin and starch metabolism inA. oryzae. The overexpression of AodevRstrongly suppressed the expression of amylase-related genes. The results of a yeast one-hybrid assay suggested that the DevR protein potentially interacts with the promoter ofamyR, which encodes a transcription factor involved in amylase production and starch utilization. This study provides new insight for further revealing the regulation mechanism of amylase production inA. oryzae.

The basic helix-loop-helix transcription factor bHLH95 affects fruit ripening and multiple metabolisms in tomato

2020 ◽  
Vol 71 (20) ◽  
pp. 6311-6327
Author(s):  
Lincheng Zhang ◽  
Jing Kang ◽  
Qiaoli Xie ◽  
Jun Gong ◽  
Hui Shen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fruit Ripening ◽  
Tomato Fruit ◽  
Soluble Sugar ◽  
Glutathione Metabolism ◽  
Bhlh Transcription Factor ◽  
Total Carotenoids ◽  
Helix Loop Helix ◽  
Tomato Fruit Ripening

Abstract Ethylene signaling pathways regulate several physiological alterations that occur during tomato fruit ripening, such as changes in colour and flavour. The mechanisms underlying the transcriptional regulation of genes in these pathways remain unclear, although the role of the MADS-box transcription factor RIN has been widely reported. Here, we describe a bHLH transcription factor, SlbHLH95, whose transcripts accumulated abundantly in breaker+4 and breaker+7 fruits compared with rin (ripening inhibitor) and Nr (never ripe) mutants. Moreover, the promoter activity of SlbHLH95 was regulated by RIN in vivo. Suppression of SlbHLH95 resulted in reduced sensitivity to ethylene, decreased accumulation of total carotenoids, and lowered glutathione content, and inhibited the expression of fruit ripening- and glutathione metabolism-related genes. Conversely, up-regulation of SlbHLH95 in wild-type tomato resulted in higher sensitivity to ethylene, increased accumulation of total carotenoids, slightly premature ripening, and elevated accumulation of glutathione, soluble sugar, and starch. Notably, overexpression of SlbHLH95 in rin led to the up-regulated expression of fruit ripening-related genes (FUL1, FUL2, SAUR69, ERF4, and CNR) and multiple glutathione metabolism-related genes (GSH1, GSH2, GSTF1, and GSTF5). These results clarified that SlbHLH95 participates in the regulation of fruit ripening and affects ethylene sensitivity and multiple metabolisms targeted by RIN in tomato.

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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