scholarly journals Id helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2686-2693 ◽  
Author(s):  
Junwon Lee ◽  
Kabsun Kim ◽  
Jung Ha Kim ◽  
Hye Mi Jin ◽  
Han Kyung Choi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Osteoclast Differentiation ◽  
Bhlh Transcription Factor ◽  
Tartrate Resistant Acid Phosphatase ◽  
Activated T Cells ◽  
Helix Loop Helix ◽  
Id Proteins ◽  
Macrophage Lineage

AbstractTumor necrosis factor (TNF)–related activation-induced cytokine (TRANCE) induces osteoclast formation from monocyte/macrophage lineage cells via various transcription factors, including the Mi transcription factor (Mitf). Here, we show that inhibitors of differentiation/DNA binding (Ids), helix-loop-helix (HLH) transcription factors, negatively regulate TRANCE-induced osteoclast differentiation. Expression levels of Id1, Id2, and Id3 genes are significantly reduced by TRANCE during osteoclastogenesis. Interestingly, overexpression of the 3 Id genes in bone marrow–derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of tartrate-resistant acid phosphatase (TRAP)–positive multinuclear osteoclasts, but it does not alter the ability of BMMs to either phagocytose or differentiate into dendritic cells (DCs). Overexpression of Id2 in BMMs attenuates the gene induction of nuclear factor of activated T cells c1 (NFATc1) and osteoclast-associated receptor (OSCAR) during TRANCE-mediated osteoclastogenesis. Furthermore, Id proteins interact with Mitf, a basic HLH (bHLH) transcription factor, and inhibit its transactivation of OSCAR, which is a costimulatory receptor expressed by osteoclast precursors, by attenuating the DNA binding ability of Mitf to the E-box site of the OSCAR promoter. Taken together, our results reveal both a new facet of negative regulation, mediated by Id proteins, as well as the mechanism whereby TRANCE signaling overcomes it, allowing osteoclastogenesis to proceed.

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.

The CIB1 Transcription Factor Regulates Light- and Heat-inducible Cell Elongation via a Two-step HLH/bHLH System

2020 ◽  
Author(s):  
Miho Ikeda ◽  
Nobutaka Mitsuda ◽  
Toru Ishizuka ◽  
Mai Satoh ◽  
Masaru Ohme-Takagi
Keyword(s):  
Transcription Factor ◽  
High Temperature ◽  
Dna Binding ◽  
Cell Elongation ◽  
Binding Activity ◽  
Bhlh Transcription Factor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Dna Binding Activity ◽  
Underlying Mechanisms

Abstract Light and high temperature promote plant cell elongation. PHYTOCHROME INTERACTING FACTOR4 (PIF4, a typical basic helix-loop-helix [bHLH] transcriptional activator) and the non-DNA-binding atypical HLH inhibitors PHYTOCHROME RAPIDLY REGULATED1 (PAR1) and LONG HYPOCOTYL IN FAR-RED 1 (HFR1) competitively regulate cell elongation in response to light conditions and high temperature. However, the underlying mechanisms have not been fully clarified. Here, we show that in Arabidopsis thaliana, the bHLH transcription factor CRYPTOCHROME-INTERACTING BASIC HELIX-LOOP-HELIX 1 (CIB1) positively regulates cell elongation under the control of PIF4, PAR1, and HFR1. Furthermore, PIF4 directly regulates CIB1 expression by interacting with its promoter, and PAR1 and HFR1 interfere with PIF4 binding to the CIB1 promoter. CIB1 activates genes that function in cell elongation, and PAR1 interferes with the DNA binding activity of CIB1, thus suppressing cell elongation. Hence, two antagonistic HLH/bHLH systems, the PIF4–PAR1/HFR1 and CIB1–PAR1 systems, regulate cell elongation in response to light and high temperature. We thus demonstrate the important role of non-DNA-binding small HLH proteins in the transcriptional regulation of cell elongation in plants.

scholarly journals Id Helix-Loop-Helix Proteins Antagonize Pax Transcription Factor Activity by Inhibiting DNA Binding

2001 ◽  
Vol 21 (2) ◽  
pp. 524-533 ◽  
Author(s):  
E. Claire Roberts ◽  
Richard W. Deed ◽  
Toshiaki Inoue ◽  
John D. Norton ◽  
Andrew D. Sharrocks
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Cellular Proliferation ◽  
Regulatory Function ◽  
Transcription Factor Family ◽  
Helix Loop Helix ◽  
Id Proteins ◽  
Proliferation And Differentiation

ABSTRACT The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation of cellular proliferation and differentiation. The major mechanism by which Id proteins are thought to inhibit differentiation is through interaction with other HLH proteins and inhibition of their DNA-binding activity. However, Id proteins have also been shown to interact with other proteins involved in regulating cellular proliferation and differentiation, suggesting a more widespread regulatory function. In this study we demonstrate functional interactions between Id proteins and members of the Pax-2/-5/-8 subfamily of paired-domain transcription factors. Members of the Pax transcription factor family have key functions in regulating several developmental processes exemplified by B lymphopoiesis, in which Pax-5 plays an essential role. Id proteins bind to Pax proteins in vitro and in vivo. Binding occurs through the paired DNA-binding domain of the Pax proteins and results in the disruption of DNA-bound complexes containing Pax-2, Pax-5, and Pax-8. In vivo, Id proteins modulate the transcriptional activity mediated by Pax-5 complexes on the B-cell-specific mb-1 promoter. Our results therefore demonstrate a novel facet of Id function in regulating cellular differentiation by functionally antagonizing the action of members of the Pax transcription factor family.

scholarly journals The transcription factor E2A drives neural differentiation in pluripotent cells

2019 ◽  
Author(s):  
Chandrika Rao ◽  
Mattias Malaguti ◽  
John O. Mason ◽  
Sally Lowell
Keyword(s):  
Transcription Factor ◽  
Neural Differentiation ◽  
Bhlh Transcription Factor ◽  
Pluripotent Cells ◽  
Neural Lineage ◽  
Binding Partner ◽  
Helix Loop Helix ◽  
Id Proteins ◽  
Mouse Cells ◽  
Extracellular Signalling

AbstractThe intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via transcriptional upregulation of Inhibitor of Differentiation (Id) factors. We have previously identified that the major binding partner of Id proteins in pluripotent cells is the basic helix-loop-helix (bHLH) transcription factor (TF), E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, including Sox1 and Foxd4, and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.

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.

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.

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