scholarly journals Atoh8 acts as a regulator of chondrocyte proliferation and differentiation in endochondral bones

2019 ◽  
Author(s):  
Nadine Schroeder ◽  
Manuela Wuelling ◽  
Daniel Hoffmann ◽  
Beate Brand-Saberi ◽  
Andrea Vortkamp
Keyword(s):  
Transcription Factor ◽  
Potential Interaction ◽  
Hypertrophic Chondrocytes ◽  
Bhlh Protein ◽  
Chondrocyte Proliferation ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Skeletal Size ◽  
Proliferation And Differentiation ◽  
Main Regulator

AbstractAtonal homolog 8 (Atoh8) is a transcription factor of the basic helix-loop-helix (bHLH) protein family, which is expressed in the cartilaginous elements of endochondral bones. To analyze its function during chondrogenesis we deleted Atoh8 in mice using a chondrocyte- (Atoh8flox/flox;Col2a1-Cre) and a germline- (Atoh8flox/flox;Prx1-Crefemale) specific Cre allele. In both strains, Atoh8 deletion leads to a reduced skeletal size of the axial and appendicular bones, but the stages of phenotypic manifestations differ. While we observed obviously shortened bones in Atoh8flox/flox;Col2a1-Cre mice only postnatally, the bones of Atoh8flox/flox;Prx1-Crefemale mice are characterized by a reduced bone length already at prenatal stages. Detailed histological and molecular investigations revealed reduced zones of proliferating and hypertrophic chondrocytes. In addition, Atoh8 deletion identified Atoh8 as a positive regulator of chondrocyte proliferation. As increased Atoh8 expression is found in the region of prehypertrophic chondrocytes where the expression of Ihh, a main regulator of chondrocyte proliferation and differentiation, is induced, we investigated a potential interaction of Atoh8 function and Ihh signaling. By activating Ihh signaling with Purmorphamine we demonstrate that Atoh8 regulates chondrocyte proliferation in parallel or downstream of Ihh signaling while it acts on the onset of hypertrophy upstream of Ihh likely by modulating Ihh expression levels.

scholarly journals Identification and Characterization of the Basic Helix-Loop-Helix Transcription Factor Family in Pinus massoniana

Forests ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1292
Author(s):  
Yu Chen ◽  
Peihuang Zhu ◽  
Fan Wu ◽  
Xiaofeng Wang ◽  
Jinfeng Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Pinus Massoniana ◽  
Pcr Analysis ◽  
Bhlh Protein ◽  
Transcription Factor Family ◽  
Masson Pine ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Bhlh Transcription Factors

The basic helix-loop-helix (bHLH) protein transcription factor family is the most widely distributed transcription factor family in eukaryotes. Members of this family play important roles in secondary metabolic biosynthesis, signal transduction, and plant resistance. Research on the bHLH family in animals is more extensive than that in plants, and members of the family in plants are classified according to the classification criteria for those in animals. To date, no research on the bHLH gene family in Pinus massoniana (Masson pine) has been reported. In this study, we identified 88 bHLH genes from four transcriptomes of Masson pine and performed bioinformatics analysis. These genes were divided into 10 groups in total. RT-PCR analysis revealed that the expression levels of the six genes increased under abiotic stress and hormone treatments. These findings will facilitate further studies on the functions of bHLH transcription factors.

scholarly journals Identification of a Basic Helix-Loop-Helix Transcription Factor Expressed in Mammary Gland Alveolar Cells and Required for Maintenance of the Differentiated State

2006 ◽  
Vol 20 (9) ◽  
pp. 2187-2198 ◽  
Author(s):  
Yan Zhao ◽  
Carina Johansson ◽  
Thai Tran ◽  
Ryan Bettencourt ◽  
Yoko Itahana ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Control Cell ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Bhlh Protein ◽  
Bhlh Transcription Factor ◽  
Alveolar Cells ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

Abstract The development of mammary glands relies on complicated signaling pathways that control cell proliferation, differentiation, and apoptotic events through transcriptional regulatory circuits. A key family of transcription factors used in mammary gland development is the helix-loop-helix/basic helix-loop-helix (HLH/bHLH) protein family. In this study, we identify Mist1 as a tissue-restricted Class II bHLH transcription factor expressed in lactating mammary glands. Mouse and human mammary glands accumulated Mist1 protein exclusively in secretory alveolar cells, and Mist1 transcripts were differentially expressed in mouse SCp2 cells induced to differentiate by addition of lactogenic hormones. Mist1 null (Mist1KO) lactating mammary glands were defective in normal lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen and premature activation of the signal transducer and activator of transcription 3 signaling pathway. These cells also failed to maintain expression of the gap junction proteins connexin26 and connexin32, leading to the loss of gap junctions. Our findings suggest that loss of Mist1 impairs the maintenance of the fully differentiated alveolar state and, for the first time, places Mist1 within the hierarchy of known HLH/bHLH proteins that control mammary epithelial cell development.

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 Target gene selectivity of the myogenic basic helix–loop–helix transcription factor myogenin in embryonic muscle

2007 ◽  
Vol 311 (2) ◽  
pp. 650-664 ◽  
Author(s):  
Judith K. Davie ◽  
Jang-Hyeon Cho ◽  
Eric Meadows ◽  
Jesse M. Flynn ◽  
Jennifer R. Knapp ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Gene ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Embryonic Muscle

Identification of transactivation and repression functions of the dioxin receptor and its basic helix-loop-helix/PAS partner factor Arnt: inducible versus constitutive modes of regulation

1994 ◽  
Vol 14 (12) ◽  
pp. 8343-8355
Author(s):  
M L Whitelaw ◽  
J A Gustafsson ◽  
L Poellinger
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Ligand Binding ◽  
Transactivation Domain ◽  
Response Element ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
C Terminus ◽  
Heterodimeric Complex ◽  
Dioxin Receptor

Gene regulation by dioxins is mediated via the dioxin receptor, a ligand-dependent basic helix-loop-helix (bHLH)/PAS transcription factor. The latent dioxin receptor responds to dioxin signalling by forming an activated heterodimeric complex with a specific bHLH partner, Arnt, an essential process for target DNA recognition. We have analyzed the transactivating potential within this heterodimeric complex by dissecting it into individual subunits, replacing the dimerization and DNA-binding bHLH motifs with heterologous zinc finger DNA-binding domains. The uncoupled Arnt chimera, maintaining 84% of Arnt residues, forms a potent and constitutive transcription factor. Chimeric proteins show that the dioxin receptor also harbors a strong transactivation domain in the C terminus, although this activity was silenced by inclusion of 82 amino acids from the central ligand-binding portion of the dioxin receptor. This central repression region conferred binding of the molecular chaperone hsp90 upon otherwise constitutive chimeras in vitro, indicating that hsp90 has the ability to mediate a cis-repressive function on distant transactivation domains. Importantly, when the ligand-binding domain of the dioxin receptor remained intact, the ability of this hsp90-binding activity to confer repression became conditional rather than irreversible. Our data are consistent with a model in which crucial activities of the dioxin receptor, such as dimerization with Arnt and transactivation, are conditionally repressed by the central ligand- and-hsp90-binding region of the receptor. In contrast, the Arnt protein appears to be free from any repressive activity. Moreover, within the context of the dioxin response element (xenobiotic response element), the C terminus of Arnt conferred a potent, dominating transactivation function onto the native bHLH heterodimeric complex. Finally, the relative transactivation potencies of the individual dioxin receptor and Arnt chimeras varied with cell type and promoter architecture, indicating that the mechanisms for transcriptional activation may differ between these two subunits and that in the native complex the transactivation pathway may be dependent upon cell-specific and promoter contexts.

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.

Myf5 is a novel early axonal marker in the mouse brain and is subjected to post-transcriptional regulation in neurons

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 319-331 ◽  
Author(s):  
P. Daubas ◽  
S. Tajbakhsh ◽  
J. Hadchouel ◽  
M. Primig ◽  
M. Buckingham
Keyword(s):  
Transcription Factor ◽  
Mouse Brain ◽  
Mrna Translation ◽  
Adult Brain ◽  
Protein Accumulation ◽  
Embryonic Mouse ◽  
Signalling Molecules ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
The Brain

Myf5 is a key basic Helix-Loop-Helix transcription factor capable of converting many non-muscle cells into muscle. Together with MyoD it is essential for initiating the skeletal muscle programme in the embryo. We previously identified unexpected restricted domains of Myf5 transcription in the embryonic mouse brain, first revealed by Myf5-nlacZ(+/)(−) embryos (Tajbakhsh, S. and Buckingham, M. (1995) Development 121, 4077–4083). We have now further characterized these Myf5 expressing neurons. Retrograde labeling with diI, and the use of a transgenic mouse line expressing lacZ under the control of Myf5 regulatory sequences, show that Myf5 transcription provides a novel axonal marker of the medial longitudinal fasciculus (mlf) and the mammillotegmental tract (mtt), the earliest longitudinal tracts to be established in the embryonic mouse brain. Tracts projecting caudally from the developing olfactory system are also labelled. nlacZ and lacZ expression persist in the adult brain, in a few ventral domains such as the mammillary bodies of the hypothalamus and the interpeduncular nucleus, potentially derived from the embryonic structures where the Myf5 gene is transcribed. To investigate the role of Myf5 in the brain, we monitored Myf5 protein accumulation by immunofluorescence and immunoblotting in neurons transcribing the gene. Although Myf5 was detected in muscle myotomal cells, it was absent in neurons. This would account for the lack of myogenic conversion in brain structures and the absence of a neural phenotype in homozygous null mutants. RT-PCR experiments show that the splicing of Myf5 primary transcripts occurs correctly in neurons, suggesting that the lack of Myf5 protein accumulation is due to regulation at the level of mRNA translation or protein stability. In the embryonic neuroepithelium, Myf5 is transcribed in differentiated neurons after the expression of neural basic Helix-Loop-Helix transcription factors. The signalling molecules Wnt1 and Sonic hedgehog, implicated in the activation of Myf5 in myogenic progenitor cells in the somite, are also produced in the viscinity of the Myf5 expression domain in the mesencephalon. We show that cells expressing Wnt1 can activate neuronal Myf5-nlacZ gene expression in dissected head explants isolated from E9.5 embryos. Furthermore, the gene encoding the basic Helix-Loop-Helix transcription factor mSim1 is expressed in adjacent cells in both the somite and the brain, suggesting that signalling molecules necessary for the activation of mSim1 as well as Myf5 are present at these different sites in the embryo. This phenomenon may be widespread and it remains to be seen how many other potentially potent regulatory genes, in addition to Myf5, when activated do not accumulate protein at inappropriate sites in the embryo.

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