Home LiteratureArticle Details
PMID: 9284045 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells.

Genes & development ·Vol. 11 ·No. 16 ·1997-08-15 ·Pages 2052-65

Boudjelal M, Taneja R, Matsubara S, Bouillet P, Dolle P, Chambon P

Abstract

We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene from P19 embryonal carcinoma cells that encodes a basic helix-loop-helix (bHLH) protein that shows the highest sequence similarities to the Drosophila Hairy and Enhancer of split and mouse Hes proteins. Stra13 does not bind to the known consensus motifs (E-box and N-box) for bHLH proteins, but can repress activated transcription (through an alpha-helix rich domain) in part by interaction with general factors of the basal transcription machinery. During mouse embryogenesis, Stra13 RNA is expressed in the neuroectoderm, and also in a number of mesodermal and endodermal derivatives. Remarkably, overexpression of Stra13 in P19 cells results in neuronal differentiation in monolayer culture, under conditions where wild-type P19 cells only undergo mesodermal/endodermal differentiation. This neuronal differentiation is accompanied by an altered expression of mesodermal and neuronal markers, indicating that Stra13 could be one of the earliest RA target genes whose expression is required for repression of mesodermal/endodermal differentiation and/or induction of neuronal differentiation when P19 cell aggregates are exposed to RA. Our results raise the possibility that Stra13 could be involved as a repressor in a number of decision events occurring during differentiation of various cell lineages.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Basic Helix-Loop-Helix Transcription Factors COS Cells Carcinoma/drug therapy,embryology,genetics Cell Differentiation/genetics Cloning, Molecular DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation, Developmental Helix-Loop-Helix Motifs/genetics Homeodomain Proteins/genetics,metabolism Mesoderm/drug effects Mice Molecular Sequence Data Neurons/drug effects Tissue Distribution Transcription Factors/genetics,metabolism Transcription, Genetic Tretinoin/metabolism,pharmacology Tumor Cells, Cultured
Chemicals
Ascl1 protein, mouse Basic Helix-Loop-Helix Transcription Factors Bhlhe40 protein, mouse DNA-Binding Proteins Homeodomain Proteins Transcription Factors Tretinoin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Boudjelal M
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université Louis Pasteur, Collège de France, Illkirch.
Taneja R
Matsubara S
Bouillet P
Dolle P
Chambon P
References (54)
54 references, click to expand
  1. Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1).
    Proc Natl Acad Sci U S A. 1978 Nov;75(11):5565-9 PMID: 281705
  2. Efficient cloning of cDNAs of retinoic acid-responsive genes in P19 embryonal carcinoma cells and characterization of a novel mouse gene, Stra1 (mouse LERK-2/Eplg2).
    Dev Biol. 1995 Aug;170(2):420-33 PMID: 7649373
  3. Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell line.
    Nature. 1982 Sep 9;299(5879):165-7 PMID: 7110336
  4. An increase in prolyl-4-hydroxylase activity occurs during the retinoic acid-induced differentiation of mouse teratocarcinoma stem cell lines F9 and P19.
    J Biol Chem. 1985 Nov 15;260(26):13893-6 PMID: 2997185
  5. Establishment of a differentiated mesodermal line from P19 EC cells expressing functional PDGF and EGF receptors.
    Exp Cell Res. 1986 Jul;165(1):229-42 PMID: 3011479
  6. Pattern abnormalities induced by ectopic expression of the Drosophila gene hairy are associated with repression of ftz transcription.
    Cell. 1987 Nov 6;51(3):405-15 PMID: 3664640
  7. Closely related transcripts encoded by the neurogenic gene complex enhancer of split of Drosophila melanogaster.
    EMBO J. 1989 Jan;8(1):203-10 PMID: 2540957
  8. Transient expression of the proto-oncogene int-1 during differentiation of P19 embryonal carcinoma cells.
    Mol Cell Biol. 1989 Mar;9(3):1357-61 PMID: 2657391
  9. The mouse homologue of the human acidic ribosomal phosphoprotein PO: a highly conserved polypeptide that is under translational control.
    Nucleic Acids Res. 1989 Aug 11;17(15):6408 PMID: 2771657
  10. The int-1 proto-oncogene is transcriptionally activated during neuroectodermal differentiation of P19 mouse embryonal carcinoma cells.
    Oncogene. 1989 Sep;4(9):1077-80 PMID: 2674852
  11. The human estrogen receptor has two independent nonacidic transcriptional activation functions.
    Cell. 1989 Nov 3;59(3):477-87 PMID: 2805068
  12. Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression.
    Mol Cell Biol. 1995 Dec;15(12):6923-31 PMID: 8524259
  13. Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects.
    Genes Dev. 1995 Dec 15;9(24):3136-48 PMID: 8543157
  14. Transcription factors 3: nuclear receptors.
    Protein Profile. 1995;2(11):1173-308 PMID: 8681033
  15. Human TAF(II28) promotes transcriptional stimulation by activation function 2 of the retinoid X receptors.
    EMBO J. 1996 Jun 17;15(12):3093-104 PMID: 8670810
  16. A decade of molecular biology of retinoic acid receptors.
    FASEB J. 1996 Jul;10(9):940-54 PMID: 8801176
  17. Identification of neurogenin, a vertebrate neuronal determination gene.
    Cell. 1996 Oct 4;87(1):43-52 PMID: 8858147
  18. Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors.
    Dev Biol. 1996 Nov 25;180(1):227-41 PMID: 8948587
  19. A posteriorising factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopus neuroectoderm.
    Development. 1996 Nov;122(11):3409-18 PMID: 8951057
  20. Vertebrate embryonic cells will become nerve cells unless told otherwise.
    Cell. 1997 Jan 10;88(1):13-7 PMID: 9019398
  21. Nuclear receptor coactivators.
    Curr Opin Cell Biol. 1997 Apr;9(2):222-32 PMID: 9069256
  22. An amino-terminal fragment of GAL4 binds DNA as a dimer.
    J Mol Biol. 1989 Oct 5;209(3):423-32 PMID: 2511324
  23. Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of beta-tubulin.
    J Biol Chem. 1990 Jan 25;265(3):1794-9 PMID: 2404018
  24. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation.
    Cell. 1990 Mar 9;60(5):733-46 PMID: 2155707
  25. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins.
    Cell. 1990 Apr 6;61(1):49-59 PMID: 2156629
  26. Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A.
    Nature. 1990 Jun 21;345(6277):729-31 PMID: 2113615
  27. Protein kinase recognition sequence motifs.
    Trends Biochem Sci. 1990 Sep;15(9):342-6 PMID: 2238044
  28. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection.
    Science. 1990 Nov 23;250(4984):1104-10 PMID: 2174572
  29. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression.
    Cell. 1991 Sep 20;66(6):1105-19 PMID: 1680563
  30. Molecular characterization of helix-loop-helix peptides.
    Science. 1992 Feb 21;255(5047):979-83 PMID: 1312255
  31. Induction and repression of mammalian achaete-scute homologue (MASH) gene expression during neuronal differentiation of P19 embryonal carcinoma cells.
    Development. 1992 Jan;114(1):75-87 PMID: 1576967
  32. Function of the c-Myc oncoprotein.
    FASEB J. 1992 Sep;6(12):3065-72 PMID: 1521738
  33. Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system.
    J Biol Chem. 1992 Oct 25;267(30):21879-85 PMID: 1400497
  34. Retinoic acid and development of the central nervous system.
    Bioessays. 1992 Jul;14(7):431-8 PMID: 1359884
  35. Expression in Escherichia coli: purification and properties of the recombinant human general transcription factor rTFIIB.
    Protein Expr Purif. 1992 Oct;3(5):374-9 PMID: 1458051
  36. Oncogenic activity of the c-Myc protein requires dimerization with Max.
    Cell. 1993 Jan 29;72(2):233-45 PMID: 8425220
  37. Distinct TFIID complexes mediate the effect of different transcriptional activators.
    EMBO J. 1993 Feb;12(2):489-99 PMID: 8440239
  38. P19 embryonal carcinoma cells.
    Int J Dev Biol. 1993 Mar;37(1):135-40 PMID: 8507558
  39. Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split.
    Eur J Biochem. 1993 Aug 1;215(3):645-52 PMID: 8354270
  40. Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system.
    Mech Dev. 1993 Aug;42(3):171-85 PMID: 8217843
  41. Functional and biochemical interaction of the HTLV-I Tax1 transactivator with TBP.
    EMBO J. 1993 Nov;12(11):4269-78 PMID: 8223437
  42. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split.
    Genes Dev. 1992 Dec;6(12B):2620-34 PMID: 1340473
  43. Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements.
    J Biol Chem. 1994 Feb 18;269(7):5150-6 PMID: 7906273
  44. Transcriptional activation: a complex puzzle with few easy pieces.
    Cell. 1994 Apr 8;77(1):5-8 PMID: 8156597
  45. Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system.
    EMBO J. 1994 Apr 15;13(8):1799-805 PMID: 7909512
  46. From embryonal carcinoma cells to neurons: the P19 pathway.
    Bioessays. 1994 May;16(5):343-8 PMID: 8024542
  47. The retinoid signaling pathway: molecular and genetic analyses.
    Semin Cell Biol. 1994 Apr;5(2):115-25 PMID: 8068884
  48. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor.
    Cell. 1994 Oct 7;79(1):107-17 PMID: 7923369
  49. Regulated expression of Wnt family members during neuroectodermal differentiation of P19 embryonal carcinoma cells: overexpression of Wnt-1 perturbs normal differentiation-specific properties.
    Dev Biol. 1994 Nov;166(1):300-10 PMID: 7958454
  50. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.
    EMBO J. 1995 May 1;14(9):2020-33 PMID: 7744009
  51. Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.
    Science. 1995 May 12;268(5212):836-44 PMID: 7754368
  52. Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system.
    Mol Cell Biol. 1995 Jul;15(7):3813-22 PMID: 7791788
  53. Conditional site-specific recombination in mammalian cells using a ligand-dependent chimeric Cre recombinase.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6991-5 PMID: 7624356
  54. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.11.16.2052
Published
1997-08-15
Pages
2052-65
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316454
Subset
IM
Databases
GENBANK
AF010305
External Links
PubMed source DOI: 10.1101/gad.11.16.2052 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2