basic helix loop helix transcription factors


Summary: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.

Top Publications

  1. Ichihashi Y, Horiguchi G, Gleissberg S, Tsukaya H. The bHLH transcription factor SPATULA controls final leaf size in Arabidopsis thaliana. Plant Cell Physiol. 2010;51:252-61 pubmed publisher
  2. Flora A, Klisch T, Schuster G, Zoghbi H. Deletion of Atoh1 disrupts Sonic Hedgehog signaling in the developing cerebellum and prevents medulloblastoma. Science. 2009;326:1424-7 pubmed publisher
    ..Our data shed light on the function of Atoh1 in postnatal cerebellar development and identify a new mechanism that can be targeted to regulate medulloblastoma formation. ..
  3. Pires N, Dolan L. Origin and diversification of basic-helix-loop-helix proteins in plants. Mol Biol Evol. 2010;27:862-74 pubmed publisher
    ..We conclude that much of the diversity of plant bHLH proteins was established in early land plants, over 440 million years ago. ..
  4. Puligilla C, Dabdoub A, Brenowitz S, Kelley M. Sox2 induces neuronal formation in the developing mammalian cochlea. J Neurosci. 2010;30:714-22 pubmed publisher
    ..Finally, we demonstrate that nonsensory cells within the cochlea retain neural competence through at least the early postnatal period. ..
  5. Fujiwara T, O Geen H, Keles S, Blahnik K, Linnemann A, Kang Y, et al. Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. Mol Cell. 2009;36:667-81 pubmed publisher
    ..These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis...
  6. Goruppi S, Iovanna J. Stress-inducible protein p8 is involved in several physiological and pathological processes. J Biol Chem. 2010;285:1577-81 pubmed publisher
    ..Understanding p8 functions will provide new opportunities for developing more effective therapeutic approaches to cancer and cardiovascular diseases. ..
  7. Ross S, Mardinly A, McCord A, Zurawski J, Cohen S, Jung C, et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron. 2010;65:886-98 pubmed publisher
    ..Our findings suggest that Bhlhb5 is required for the survival of a specific population of inhibitory interneurons that regulate pruritus, and provide evidence that the loss of inhibitory synaptic input results in abnormal itch. ..
  8. Levskaya A, Weiner O, Lim W, Voigt C. Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature. 2009;461:997-1001 pubmed publisher
  9. Cras Méneur C, Li L, Kopan R, Permutt M. Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window. Genes Dev. 2009;23:2088-101 pubmed publisher

More Information


  1. Brend T, Holley S. Expression of the oscillating gene her1 is directly regulated by Hairy/Enhancer of Split, T-box, and Suppressor of Hairless proteins in the zebrafish segmentation clock. Dev Dyn. 2009;238:2745-59 pubmed publisher
    ..These data provide the foundation for a precise description of the regulatory grammar that defines oscillating gene expression in the zebrafish segmentation clock...
  2. Hirabayashi Y, Suzki N, Tsuboi M, Endo T, Toyoda T, Shinga J, et al. Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron. 2009;63:600-13 pubmed publisher
    ..Moreover, PcG was found to repress the promoter of the proneural gene neurogenin1 in a developmental-stage-dependent manner. These results demonstrate a role of PcG: the temporal regulation of NPC fate. ..
  3. Beck K, Peak M, Ota T, Nemazee D, Murre C. Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci. J Exp Med. 2009;206:2271-84 pubmed publisher
    ..We propose that in the pre-B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes. ..
  4. Rundqvist H, Johnson R. Hypoxia and metastasis in breast cancer. Curr Top Microbiol Immunol. 2010;345:121-39 pubmed publisher
    ..In this review we summarize the evidence for a role for hypoxic response in the biology of metastasis, with a particular emphasis on the metastasis of breast cancer and the function of the hypoxia inducible factor (HIF). ..
  5. Diebold I, Flügel D, Becht S, BelAiba R, Bonello S, Hess J, et al. The hypoxia-inducible factor-2alpha is stabilized by oxidative stress involving NOX4. Antioxid Redox Signal. 2010;13:425-36 pubmed publisher
    ..Together, these findings present the first evidence that HIF-2alpha is critically involved in the ROS-regulated vascular remodeling processes. ..
  6. Jennings A, Carroll W. Quantification of oligodendrocyte progenitor cells in human and cat optic nerve: implications for endogenous repair in multiple sclerosis. Glia. 2010;58:1425-36 pubmed publisher
    ..The finding that NG2cells are not abundant, particularly relative to oligodendrocytes, may have implications for efforts to enhance endogenous repair in MS. ..
  7. Dizon M, SZELE F, Kessler J. Hypoxia-ischemia induces an endogenous reparative response by local neural progenitors in the postnatal mouse telencephalon. Dev Neurosci. 2010;32:173-83 pubmed publisher
    ..Thus, an endogenous regenerative oligodendroglial response to postnatal hypoxia-ischemia occurs locally, with minimal long-distance contribution by cells of the SVZ. ..
  8. Yang H, Silva A, Koyano Nakagawa N, McLoon S. Progenitor cell maturation in the developing vertebrate retina. Dev Dyn. 2009;238:2823-36 pubmed publisher
    ..Our results show that the preneurogenic-to-neurogenic transition is a highly organized unidirectional step made in unison by neighboring cells. ..
  9. Wang G, Kauri L, Patrick C, Bareggi M, Rosenberg L, Scott F. Enhanced islet expansion by beta-cell proliferation in young diabetes-prone rats fed a protective diet. J Cell Physiol. 2010;224:501-8 pubmed publisher
    ..Thus, in BBdp rats fed a protective HC diet, beta-cell expansion is enhanced through increased beta-cell proliferation and stimulation of islet neogenesis. ..
  10. Utting J, Flanagan A, Brandao Burch A, Orriss I, Arnett T. Hypoxia stimulates osteoclast formation from human peripheral blood. Cell Biochem Funct. 2010;28:374-80 pubmed publisher
  11. Soria V, Martínez Amorós E, Escaramis G, Valero J, Pérez Egea R, Garcia C, et al. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology. 2010;35:1279-89 pubmed publisher
    ..Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity. ..
  12. Tormos K, Chandel N. Inter-connection between mitochondria and HIFs. J Cell Mol Med. 2010;14:795-804 pubmed publisher
    ..In this review, we examine the evidence that mitochondria and HIFs are intimately connected to regulate each other resulting in appropriate responses to hypoxia. ..
  13. Wang C, Yao N, Lu C, Li D, Ma X. Mouse microRNA-124 regulates the expression of Hes1 in P19 cells. Front Biosci (Elite Ed). 2010;2:127-32 pubmed
    ..Thus, our results indicate that miR-124 regulates the expression of Hes-1 at the post-transcriptional level and is involved in the retinoic acid-induced neuronal differentiation of P19 cells. ..
  14. Westhoff B, Colaluca I, D ario G, Donzelli M, Tosoni D, Volorio S, et al. Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci U S A. 2009;106:22293-8 pubmed publisher
    ..Our results show that the deregulation of the Notch pathway is a relatively frequent event in NSCLCs and suggest that it might represent a possible target for molecular therapies in these tumors. ..
  15. Kerns D, Vong G, Barley K, Dracheva S, Katsel P, CASACCIA P, et al. Gene expression abnormalities and oligodendrocyte deficits in the internal capsule in schizophrenia. Schizophr Res. 2010;120:150-8 pubmed publisher
    ..These data are consistent with the hypothesis that Ol and myelin deficits in SZ involve a failure of Ol precursors to appropriately exit the cell cycle in order to differentiate and mature into myelinating Ols. ..
  16. Xing Q, Ye Q, Fan M, Zhou Y, Xu Q, Sandham A. Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling. J Cell Physiol. 2010;225:106-14 pubmed publisher
    ..Together, these findings suggest that P-LPS inhibits osteoblast differentiation by promoting the expression of Notch target genes and suppressing canonical Wnt/beta-catenin signaling. ..
  17. Shimizu T, Nakazawa M, Kani S, Bae Y, Shimizu T, Kageyama R, et al. Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain. Development. 2010;137:1875-85 pubmed publisher
    ..Our findings reveal that Fezf1 and Fezf2 control differentiation of neural stem cells by repressing Hes5 and, in turn, by derepressing neurogenin 2 in the forebrain. ..
  18. Ishimatsu K, Takamatsu A, Takeda H. Emergence of traveling waves in the zebrafish segmentation clock. Development. 2010;137:1595-9 pubmed publisher
    ..Furthermore, we suggest that Fgf has an essential role in establishing the period gradient that is required for the her1 spatial oscillation pattern at the emergence of the traveling wave...
  19. Matsuda M, Chitnis A. Atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the posterior lateral line primordium in zebrafish. Development. 2010;137:3477-87 pubmed publisher
    ..Together, our observations reveal a genetic regulatory network that explains why atoh1a expression must be restricted by Notch signaling for effective morphogenesis of the pLLp. ..
  20. Santisteban P, Recacha P, Metzger D, Zaret K. Dynamic expression of Groucho-related genes Grg1 and Grg3 in foregut endoderm and antagonism of differentiation. Dev Dyn. 2010;239:980-6 pubmed publisher
    ..We suggest that Grg expression in the endoderm helps suppress the liver program and find that endodermal competence involves a balance between activators and corepressors. ..
  21. Probst Cousin S, Neundörfer B, Heuss D. Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors. Neuromuscul Disord. 2010;20:192-7 pubmed publisher
    ..These observations suggest that the upregulation of hypoxia-related proteins may represent an adaptation mechanism of neuromuscular tissues to immune mediated deprivation of the blood supply...
  22. Skowronska Krawczyk D, Chiodini F, Ebeling M, Alliod C, Kundzewicz A, Castro D, et al. Conserved regulatory sequences in Atoh7 mediate non-conserved regulatory responses in retina ontogenesis. Development. 2009;136:3767-77 pubmed publisher
    ..In summary, we show how highly conserved regulatory elements are put to use in mediating non-conserved functions and creating interspecies neuronal diversity. ..
  23. Luo W, Zhong J, Chang R, Hu H, Pandey A, Semenza G. Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1alpha but Not HIF-2alpha. J Biol Chem. 2010;285:3651-63 pubmed publisher
    ..Thus, Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of HIF-1alpha but not HIF-2alpha protein. ..
  24. Manthey C, Mern D, Gutmann A, Zielinski A, Herz C, Lassmann S, et al. Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells. BMC Cell Biol. 2010;11:2 pubmed publisher
    ..Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness. ..
  25. Monastirioti M, Giagtzoglou N, Koumbanakis K, Zacharioudaki E, Deligiannaki M, Wech I, et al. Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and larval neurogenesis. Development. 2010;137:191-201 pubmed publisher
    ..The availability of Hey as a Notch readout has allowed us to study Notch signalling during the genesis of secondary neurons in the larval central nervous system. ..
  26. Aguado Llera D, Goormaghtigh E, De Geest N, Quan X, Prieto A, Hassan B, et al. The basic helix-loop-helix region of human neurogenin 1 is a monomeric natively unfolded protein which forms a "fuzzy" complex upon DNA binding. Biochemistry. 2010;49:1577-89 pubmed publisher
    ..The affinities of bHLHN for both DNA boxes were smaller than those of other bHLH domains, which might explain why the protein-DNA complexes were not fully folded. ..
  27. Girin T, Stephenson P, Goldsack C, Kempin S, Perez A, Pires N, et al. Brassicaceae INDEHISCENT genes specify valve margin cell fate and repress replum formation. Plant J. 2010;63:329-38 pubmed publisher
    ..An enlargement of replum size was also observed in the Arabidopsis ind mutant suggesting a general role of Brassicaceae IND genes in preventing valve margin cells from adopting replum identity. ..
  28. Kani S, Bae Y, Shimizu T, Tanabe K, Satou C, Parsons M, et al. Proneural gene-linked neurogenesis in zebrafish cerebellum. Dev Biol. 2010;343:1-17 pubmed publisher
    ..Our data indicate that proneural gene-linked neurogenesis is evolutionarily conserved in the cerebellum among vertebrates, and that the continuously generated neurons help remodel neural circuits in the adult zebrafish cerebellum. ..
  29. Sundberg M, Skottman H, Suuronen R, Narkilahti S. Production and isolation of NG2+ oligodendrocyte precursors from human embryonic stem cells in defined serum-free medium. Stem Cell Res. 2010;5:91-103 pubmed publisher
    ..Importantly, these NG2(+) spheres were free of pluripotent Tra1-81, Oct-4, and CD326-positive hESCs. Thus, this method is suitable for the efficient production of OPCs and in the future for therapeutic graft production. ..
  30. Wang X, Fu Y, Chen X, Ye J, Lu B, Ye F, et al. The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. J Cancer Res Clin Oncol. 2010;136:989-96 pubmed publisher
    ..The expressions of bHLH gene HES1 and HES5 are increased in advanced ovarian serous adenocarcinomas, and HES1 high-expression probably is a potential poor prognostic factor for the patients. ..
  31. Takano Maruyama M, Chen Y, Gaufo G. Placodal sensory ganglia coordinate the formation of the cranial visceral motor pathway. Dev Dyn. 2010;239:1155-61 pubmed publisher
  32. Decarlo K, Yang S, Emley A, Wajapeyee N, Green M, Mahalingam M. Oncogenic BRAF-positive dysplastic nevi and the tumor suppressor IGFBP7--challenging the concept of dysplastic nevi as precursor lesions?. Hum Pathol. 2010;41:886-94 pubmed publisher
  33. Henley B, McDermott K. The expression of neuroepithelial cell fate determinants in rat spinal cord development. J Mol Neurosci. 2010;42:28-34 pubmed publisher
    ..By understanding how neural stem cells are regulated in spinal cord development in vivo, we may gain insight of relevance to cell replacement strategies to treat spinal cord injuries. ..
  34. Kim T, Hemberg M, Gray J, Costa A, Bear D, Wu J, et al. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010;465:182-7 pubmed publisher
    ..These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis. ..
  35. Hu W, Gauthier L, Baibakov B, Jimenez Movilla M, Dean J. FIGLA, a basic helix-loop-helix transcription factor, balances sexually dimorphic gene expression in postnatal oocytes. Mol Cell Biol. 2010;30:3661-71 pubmed publisher
    ..These data demonstrate that physiological expression of Figla plays a critical dual role in activation of oocyte-associated genes and repression of sperm-associated genes during normal postnatal oogenesis. ..
  36. Yang J, Ledaki I, Turley H, Gatter K, Montero J, Li J, et al. Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases. Ann N Y Acad Sci. 2009;1177:185-97 pubmed publisher
    ..This provides a new mechanism for regulation of the response to hypoxia. ..
  37. Jin K, Jiang H, Mo Z, Xiang M. Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors. J Neurosci. 2010;30:11902-16 pubmed publisher
  38. Kim W, Meliton V, Tetradis S, Weinmaster G, Hahn T, Carlson M, et al. Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells. J Bone Miner Res. 2010;25:782-95 pubmed publisher
    ..Finally, HES-1 and HEY-1 siRNA transfection significantly inhibited 20S-induced osteogenic genes, suggesting that the pro-osteogenic effects of 20S are regulated in part by HES-1 and HEY-1. ..
  39. Dehne T, Schenk R, Perka C, Morawietz L, Pruss A, Sittinger M, et al. Gene expression profiling of primary human articular chondrocytes in high-density micromasses reveals patterns of recovery, maintenance, re- and dedifferentiation. Gene. 2010;462:8-17 pubmed publisher
    ..Cultivation longer than 6 weeks leads to progressing dedifferentiation of chondrocytes that should be considered on long-term evaluations. ..
  40. Chen L, Lopes J. Multiple bHLH proteins regulate CIT2 expression in Saccharomyces cerevisiae. Yeast. 2010;27:345-59 pubmed publisher
    ..Collectively, these results support the model that yeast bHLH proteins coordinate different biological pathways. ..
  41. Wellnitz S, Lesniak D, Gerling G, Lumpkin E. The regularity of sustained firing reveals two populations of slowly adapting touch receptors in mouse hairy skin. J Neurophysiol. 2010;103:3378-88 pubmed publisher
  42. Galli A, Robay D, Osterwalder M, Bao X, Bénazet J, Tariq M, et al. Distinct roles of Hand2 in initiating polarity and posterior Shh expression during the onset of mouse limb bud development. PLoS Genet. 2010;6:e1000901 pubmed publisher
    ..Our study uncovers essential components of the transcriptional machinery and key interactions that set-up limb bud asymmetry upstream of establishing the SHH signaling limb bud organizer. ..
  43. Holler K, Hendershot T, Troy S, Vincentz J, Firulli A, Howard M. Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development. Dev Biol. 2010;341:291-304 pubmed publisher
    ..Our genetic model has made it possible to investigate the molecular genetics of neural crest contributions to outflow tract morphogenesis and cell differentiation. ..
  44. Dong Y, Jesse A, Kohn A, Gunnell L, Honjo T, Zuscik M, et al. RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development. Development. 2010;137:1461-71 pubmed publisher
    ..Finally, Hes1 was identified as an RBPjkappa-dependent Notch target gene important for MPC maintenance and the suppression of in vitro chondrogenesis. ..
  45. Lee J, Wada T, Febbraio M, He J, Matsubara T, Lee M, et al. A novel role for the dioxin receptor in fatty acid metabolism and hepatic steatosis. Gastroenterology. 2010;139:653-63 pubmed publisher
    ..Results from this study may help to establish AhR and its target CD36 as novel therapeutic and preventive targets for fatty liver disease. ..
  46. Haddady S, Low H, Billings Gagliardi S, Riskind P, Schwartz W. Pregnancy modulates precursor cell proliferation in a murine model of focal demyelination. Neuroscience. 2010;167:656-64 pubmed publisher
  47. Hyvärinen J, Hassinen I, Sormunen R, Maki J, Kivirikko K, Koivunen P, et al. Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury. J Biol Chem. 2010;285:13646-57 pubmed publisher
    ..Our data suggest that chronic stabilization of Hif-1alpha and Hif-2alpha by genetic knockdown of Hif-p4h-2 promotes cardioprotection by induction of many genes involved in glucose metabolism, cardiac function, and blood pressure. ..
  48. Chaplin N, Tendeng C, Wingate R. Absence of an external germinal layer in zebrafish and shark reveals a distinct, anamniote ground plan of cerebellum development. J Neurosci. 2010;30:3048-57 pubmed publisher
    ..We show that these anamniotes share a common ground plan of granule cell production that does not include an external germinal layer. ..
  49. Wenger R, Hoogewijs D. Regulated oxygen sensing by protein hydroxylation in renal erythropoietin-producing cells. Am J Physiol Renal Physiol. 2010;298:F1287-96 pubmed publisher
  50. Bougatef F, Menashi S, Khayati F, Naimi B, Porcher R, Podgorniak M, et al. EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. PLoS ONE. 2010;5:e12265 pubmed publisher
    ..The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion. ..
  51. Gruber M, Mathew L, Runge A, Garcia J, Simon M. EPAS1 Is Required for Spermatogenesis in the Postnatal Mouse Testis. Biol Reprod. 2010;82:1227-36 pubmed publisher
    ..We conclude that low O(2) levels in the male gonad regulate germ cell homeostasis in this organ via EPAS1...
  52. Richter R, Behringer C, Müller I, Schwechheimer C. The GATA-type transcription factors GNC and GNL/CGA1 repress gibberellin signaling downstream from DELLA proteins and PHYTOCHROME-INTERACTING FACTORS. Genes Dev. 2010;24:2093-104 pubmed publisher
    ..These findings, together with the fact that gnc and gnl loss-of-function mutations suppress ga1 phenotypes, support the hypothesis that GNC and GNL are important repressors of GA signaling downstream from the DELLA and PIF regulators. ..