Misexpression of basic helix-loop-helix genes in the murine cerebral cortex affects cell fate choices and neuronal survival

Development ◽  
2000 ◽  
Vol 127 (14) ◽  
pp. 3021-3030 ◽  
Author(s):  
L. Cai ◽  
E.M. Morrow ◽  
C.L. Cepko
Keyword(s):  
Cerebral Cortex ◽  
Cell Fate ◽  
Neuronal Survival ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Infected Cells ◽  
Glial Fate

To investigate the role(s) of basic helix-loop-helix genes (bHLH) genes in the developing murine cerebral cortex, Mash1, Math2, Math3, Neurogenin1 (Ngn1), Ngn2, NeuroD, NeuroD2 and Id1 were transduced in vivo into the embryonic and postnatal cerebral cortex using retrovirus vectors. The morphology and location of infected cells were analyzed at postnatal stages. The data indicate that a subset of bHLH genes are capable of regulating the choice of neuronal versus glial fate and that, when misexpressed, they can be deleterious to the survival of differentiating neurons, but not glia.

scholarly journals The Drosophila Basic Helix-Loop-Helix Protein DIMMED Directly Activates PHM, a Gene Encoding a Neuropeptide-Amidating Enzyme

2007 ◽  
Vol 28 (1) ◽  
pp. 410-421 ◽  
Author(s):  
Dongkook Park ◽  
Orie T. Shafer ◽  
Stacie P. Shepherd ◽  
Hyunsuk Suh ◽  
Jennifer S. Trigg ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Activation ◽  
Regulatory Region ◽  
Total Activity ◽  
Bhlh Protein ◽  
Hek 293 ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Boxes

ABSTRACT The basic helix-loop-helix (bHLH) protein DIMMED (DIMM) supports the differentiation of secretory properties in numerous peptidergic cells of Drosophila melanogaster. DIMM is coexpressed with diverse amidated neuropeptides and with the amidating enzyme peptidylglycine α-hydroxylating monooxygenase (PHM) in approximately 300 cells of the late embryo. Here we confirm that DIMM has transcription factor activity in transfected HEK 293 cells and that the PHM gene is a direct target. The mammalian DIMM orthologue MIST1 also transactivated the PHM gene. DIMM activity was dependent on the basic region of the protein and on the sequences of three E-box sites within PHM's first intron; the sites make different contributions to the total activity. These data suggest a model whereby the three E boxes interact cooperatively and independently to produce high PHM transcriptional activation. This DIMM-controlled PHM regulatory region displayed similar properties in vivo. Spatially, its expression mirrored that of the DIMM protein, and its activity was largely dependent on dimm. Further, in vivo expression was highly dependent on the sequences of the same three E boxes. This study supports the hypothesis that DIMM is a master regulator of a peptidergic cell fate in Drosophila and provides a detailed transcriptional mechanism of DIMM action on a defined target gene.

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.

A novel basic helix-loop-helix protein is expressed in muscle attachment sites of the Drosophila epidermis

1994 ◽  
Vol 14 (6) ◽  
pp. 4145-4154
Author(s):  
P Armand ◽  
A C Knapp ◽  
A J Hirsch ◽  
E F Wieschaus ◽  
M D Cole
Keyword(s):  
Distinct Pattern ◽  
Bhlh Protein ◽  
Muscle Attachment ◽  
Muscle Creatine Kinase ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Attachment Sites ◽  
Bhlh Genes ◽  
Somatic Muscles ◽  
Muscle Attachment Sites

We have found that a novel basic helix-loop-helix (bHLH) protein is expressed almost exclusively in the epidermal attachments sites for the somatic muscles of Drosophila melanogaster. A Drosophila cDNA library was screened with radioactively labeled E12 protein, which can dimerize with many HLH proteins. One clone that emerged from this screen encoded a previously unknown protein of 360 amino acids, named delilah, that contains both basic and HLH domains, similar to a group of cellular transcription factors implicated in cell type determination. Delilah protein formed heterodimers with E12 that bind to the muscle creatine kinase promoter. In situ hybridization with the delilah cDNA localized the expression of the gene to a subset of cells in the epidermis which form a distinct pattern involving both the segmental boundaries and intrasegmental clusters. This pattern was coincident with the known sites of attachment of the somatic muscles to tendon cells in the epidermis. delilah expression persists in snail mutant embryos which lack mesoderm, indicating that expression of the gene was not induced by attachment of the underlying muscles. The similarity of this gene to other bHLH genes suggests that it plays an important role in the differentiation of epidermal cells into muscle attachment sites.

Overexpression of PtrbHLH, a basic helix-loop-helix transcription factor from Poncirus trifoliata, confers enhanced cold tolerance in pummelo (Citrus grandis) by modulation of H2O2 level via regulating a CAT gene

2019 ◽  
Author(s):  
Jingjing Geng ◽  
Tonglu Wei ◽  
Yue Wang ◽  
Xiaosan Huang ◽  
Ji-Hong Liu
Keyword(s):  
Cold Tolerance ◽  
Cold Treatment ◽  
Poncirus Trifoliata ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Transgenic Lines ◽  
Elevated Activity ◽  
H2o2 Level ◽  
Cat Gene

Abstract The basic helix-loop-helix (bHLH) family of transcription factors (TFs) plays a crucial role in regulating plant response to abiotic stress by targeting a large spectrum of stress-responsive genes. However, the physiological mechanisms underlying the TF-mediated stress response are still poorly understood for most of the bHLH genes. In this study, transgenic pummelo (Citrus grandis) plants overexpressing PtrbHLH, a TF previously identified from Poncirus trifoliata, were generated via Agrobacterium-mediated transformation. In comparison with the wild-type plants, the transgenic lines exhibited significantly lower electrolyte leakage and malondialdehyde content after cold treatment, thereby resulting in a more tolerant phenotype. Meanwhile, the transgenic lines accumulated dramatically lower reactive oxygen species (ROS) levels, consistent with elevated activity and expression levels of antioxidant enzymes (genes), including catalase (CAT), peroxidase and superoxide dismutase. In addition, PtrbHLH was shown to specifically bind to and activate the promoter of PtrCAT gene. Taken together, these results demonstrated that overexpression of PtrbHLH leads to enhanced cold tolerance in transgenic pummelo, which may be due, at least partly, to modulation of ROS levels by regulating the CAT gene.

The Basic Helix-Loop-Helix TAL1/SCL and Its Partners E47 and LMO2 Act Upstream of the VE-Cadherin Gene in Endothelial Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1795-1795
Author(s):  
Virginie Deleuze ◽  
Elias Chalhoub ◽  
Rawan El-Hajj ◽  
Christiane Dohet ◽  
Mikael Le Clech ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ectopic Expression ◽  
Cell Junctions ◽  
Small Interfering Rnas ◽  
Hek 293 ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Cell Cell

Abstract The basic helix-loop-helix protein TAL-1/SCL, essential for the formation of the hematopoietic system, is also required for vascular development and more particularly for embryonic angiogenesis. We previously reported that TAL-1 acts as a positive factor for post-natal angiogenesis by stimulating endothelial morphogenesis. To understand how TAL-1 modulates angiogenesis, we investigated the functional consequences of TAL-1 silencing, mediated by small-interfering RNAs, in human primary endothelial cells (ECs). We found that TAL-1 knockdown impaired in vitro EC tubulomorphogenesis (in 2-D on Matrigel or 3-D in collagen I gel), with the notable absence of cell-cell contacts, a prerequisite for morphogenesis initiation. This cellular deficiency was associated with a dramatic reduction in the vascular-endothelial (VE)-cadherin at intercellular junctions, the major component of endothelial adherens junctions. In contrast, PECAM (or CD31) was present at cell-cell junctions at the same levels as control cells. Importantly, silencing of two known TAL-1-partners in hematopoietic cells, E47 or LMO2, produce the same effects as TAL-1. Accordingly, silencing of TAL-1, as well as E47 and LMO2, provoked down-regulation of VE-cadherin at both the mRNA and protein levels. Transient transfection experiments in HUVECs showed that TAL-1 and E47 regulate the VE-cadherin promoter through a specialized E-box element. Finally, endogenous VE-cadherin transcription could be directly activated in non-endothelial HEK-293 cells that neither express TAL-1 or LMO2, by the sole concomitant ectopic expression of TAL-1, E47 and LMO2. Overall, our data demonstrate that a multiprotein complex containing at least TAL-1, LMO2 and E47 act upstream of the VE-cadherin gene. We are currently performing chromatin immunoprecipitation (ChIP) to investigate whether the TAL-1-containing complex binds in vivo the VE-cadherin promoter. This study identifies VE-cadherin as an upstream TAL-1-target gene in the endothelial lineage, and provides a first clue in TAL-1 function in the control of angiogenesis.

A genome-wide identification and classification of basic helix-loop-helix genes in the jewel wasp, Nasonia vitripennis (Hymenoptera: Pteromalidae)

Genome ◽  
2014 ◽  
Vol 57 (10) ◽  
pp. 525-536 ◽  
Author(s):  
Xiao-Ting Liu ◽  
Yong Wang ◽  
Xu-Hua Wang ◽  
Xia-Fang Tao ◽  
Qin Yao ◽  
...  
Keyword(s):  
Heart Development ◽  
Family Members ◽  
Insect Species ◽  
Structural Domain ◽  
Nasonia Vitripennis ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
A Genome ◽  
Bhlh Genes ◽  
Bhlh Proteins

Basic helix-loop-helix (bHLH) proteins are highly conserved DNA-binding transcription factors of a large superfamily. Animal bHLH proteins play important regulatory roles in various developmental processes such as neurogenesis, myogenesis, heart development, and hematopoiesis. The jewel wasp (Nasonia vitripennis) is a good model organism of hymenoptera insects for studies of developmental and evolutionary genetics. In this study, we identified 48 bHLH genes in the genome of N. vitripennis. According to phylogenetic analysis, based on N. vitripennis bHLH (NvbHLH) motif sequences and structural domain distribution in their full-length protein sequences, the identified NvbHLH genes were classified into 36 bHLH families with 19, 12, 9, 1, 6, and 1 member(s) in groups A, B, C, D, E, and F, respectively. Our classification to the identified NvbHLH family members confirms GenBank annotations for 21 of the 48 NvbHLH proteins and provides useful information for further characterization and annotation of the remaining 27 NvbHLH proteins. Compared to other insect species, N. vitripennis has the lowest number of bHLH family members. No NvbHLH members have been found in the families Net, MyoRa, and PTFa, while all other insect species have at least one member in each of the families. These data constitute a solid basis for further investigations into the functions of bHLH proteins in developmental regulation of N. vitripennis.

scholarly journals MondoA, a Novel Basic Helix-Loop-Helix–Leucine Zipper Transcriptional Activator That Constitutes a Positive Branch of a Max-Like Network

2000 ◽  
Vol 20 (23) ◽  
pp. 8845-8854 ◽  
Author(s):  
Andrew N. Billin ◽  
Alanna L. Eilers ◽  
Kathryn L. Coulter ◽  
Jennifer S. Logan ◽  
Donald E. Ayer
Keyword(s):  
Transcriptional Activation ◽  
Nuclear Export ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
Functional Characterization ◽  
Nuclear Accumulation ◽  
Cytoplasmic Localization ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

ABSTRACT Max is a common dimerization partner for a family of transcription factors (Myc, Mad [or Mxi]), and Mnt [or Rox] proteins) that regulate cell growth, proliferation, and apoptosis. We recently characterized a novel Max-like protein, Mlx, which interacts with Mad1 and Mad4. Here we describe the cloning and functional characterization of a new family of basic helix-loop-helix–leucine zipper heterodimeric partners for Mlx termed the Mondo family. MondoA forms homodimers weakly and does not interact with Max or members of the Myc or Mad families. MondoA and Mlx associate in vivo, and surprisingly, they are localized primarily to the cytoplasm of cultured mammalian cells. Treatment of cells with the nuclear export inhibitor leptomycin B results in the nuclear accumulation of MondoA and Mlx, demonstrating that they shuttle between the cytoplasmic and nuclear compartments rather than having exclusively cytoplasmic localization. MondoA preferentially forms heterodimers with Mlx, and this heterocomplex can bind to, and activate transcription from, CACGTG E-boxes when targeted to the nucleus via a heterologous nuclear localization signal. The amino termini of the Mondo proteins are highly conserved among family members and contain separable and autonomous cytoplasmic localization and transcription activation domains. Therefore, Mlx can mediate transcriptional repression in conjunction with the Mad family and can mediate transcriptional activation via the Mondo family. We propose that Mlx, like Max, functions as the center of a transcription factor network.

scholarly journals Transcription factor Tcf4 is the preferred heterodimerization partner for Olig2 in oligodendrocytes and required for differentiation

2020 ◽  
Vol 48 (9) ◽  
pp. 4839-4857 ◽  
Author(s):  
Miriam Wedel ◽  
Franziska Fröb ◽  
Olga Elsesser ◽  
Marie-Theres Wittmann ◽  
D Chichung Lie ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Physical Interaction ◽  
Functional Studies ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Mouse Mutants ◽  
Id Proteins ◽  
A Cell ◽  
Oligodendrocyte Development

Abstract Development of oligodendrocytes and myelin formation in the vertebrate central nervous system is under control of several basic helix-loop-helix transcription factors such as Olig2, Ascl1, Hes5 and the Id proteins. The class I basic helix-loop-helix proteins Tcf3, Tcf4 and Tcf12 represent potential heterodimerization partners and functional modulators for all, but have not been investigated in oligodendrocytes so far. Using mouse mutants, organotypic slice and primary cell cultures we here show that Tcf4 is required in a cell-autonomous manner for proper terminal differentiation and myelination in vivo and ex vivo. Partial compensation is provided by the paralogous Tcf3, but not Tcf12. On the mechanistic level Tcf4 was identified as the preferred heterodimerization partner of the central regulator of oligodendrocyte development Olig2. Both genetic studies in the mouse as well as functional studies on enhancer regions of myelin genes confirmed the relevance of this physical interaction for oligodendrocyte differentiation. Considering that alterations in TCF4 are associated with syndromic and non-syndromic forms of intellectual disability, schizophrenia and autism in humans, our findings point to the possibility of an oligodendroglial contribution to these disorders.

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