Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 7 June 1996:
Vol. 272. no. 5267, pp. 1476 - 1480
DOI: 10.1126/science.272.5267.1476

Reports

Inhibition of Myogenic bHLH and MEF2 Transcription Factors by the bHLH Protein Twist

Douglas B. Spicer, James Rhee, Wang L. Cheung, Andrew B. Lassar *

The myogenic basic helix-loop-helix (bHLH) and MEF2 transcription factors are expressed in the myotome of developing somites and cooperatively activate skeletal muscle gene expression. The bHLH protein Twist is expressed throughout the epithelial somite and is subsequently excluded from the myotome. Ectopically expressed mouse Twist (Mtwist) was shown to inhibit myogenesis by blocking DNA binding by MyoD, by titrating E proteins, and by inhibiting trans-activation by MEF2. For inhibition of MEF2, Mtwist required heterodimerization with E proteins and an intact basic domain and carboxyl-terminus. Thus, Mtwist inhibits both families of myogenic regulators and may regulate myotome formation temporally or spatially.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
* To whom correspondence should be addressed. E-mail: lassarab{at}warren.med.harvard.edu



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Twist-1 regulates the miR-199a/214 cluster during development.
Y.-B. Lee, I. Bantounas, D.-Y. Lee, L. Phylactou, M. A. Caldwell, and J. B. Uney (2009)
Nucleic Acids Res. 37, 123-128
   Abstract »    Full Text »    PDF »
Rho/Rho-associated Kinase Signal Regulates Myogenic Differentiation via Myocardin-related Transcription Factor-A/Smad-dependent Transcription of the Id3 Gene.
K. Iwasaki, K. Hayashi, T. Fujioka, and K. Sobue (2008)
J. Biol. Chem. 283, 21230-21241
   Abstract »    Full Text »    PDF »
Mechanism of Transcriptional Activation by the Proto-oncogene Twist1.
K. B. Laursen, E. Mielke, P. Iannaccone, and E.-M. Fuchtbauer (2007)
J. Biol. Chem. 282, 34623-34633
   Abstract »    Full Text »    PDF »
The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes.
A. J. Bingham, L. Ooi, L. Kozera, E. White, and I. C. Wood (2007)
Mol. Cell. Biol. 27, 4082-4092
   Abstract »    Full Text »    PDF »
Comparative roles of Twist-1 and Id1 in transcriptional regulation by BMP signaling.
M. Hayashi, K. Nimura, K. Kashiwagi, T. Harada, K. Takaoka, H. Kato, K. Tamai, and Y. Kaneda (2007)
J. Cell Sci. 120, 1350-1357
   Abstract »    Full Text »    PDF »
Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel.
G. Z. Cheng, J. Chan, Q. Wang, W. Zhang, C. D. Sun, and L.-H. Wang (2007)
Cancer Res. 67, 1979-1987
   Abstract »    Full Text »    PDF »
Twist mediates suppression of inflammation by type I IFNs and Axl.
M. N. Sharif, D. Sosic, C. V. Rothlin, E. Kelly, G. Lemke, E. N. Olson, and L. B. Ivashkiv (2006)
J. Exp. Med. 203, 1891-1901
   Abstract »    Full Text »    PDF »
Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells.
R. Saab, J. L. Bills, A. P. Miceli, C. M. Anderson, J. D. Khoury, D. W. Fry, F. Navid, P. J. Houghton, and S. X. Skapek (2006)
Mol. Cancer Ther. 5, 1299-1308
   Abstract »    Full Text »    PDF »
The Wnt-inducible Transcription Factor Twist1 Inhibits Chondrogenesis.
M. I. Reinhold, R. M. Kapadia, Z. Liao, and M. C. Naski (2006)
J. Biol. Chem. 281, 1381-1388
   Abstract »    Full Text »    PDF »
Adult Myogenesis in Drosophila melanogaster Can Proceed Independently of Myocyte Enhancer Factor-2.
P. W. Baker, K. K. K. Tanaka, N. Klitgord, and R. M. Cripps (2005)
Genetics 170, 1747-1759
   Abstract »    Full Text »    PDF »
Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target.
W. K. Kwok, M.-T. Ling, T.-W. Lee, T. C.M. Lau, C. Zhou, X. Zhang, C. W. Chua, K. W. Chan, F. L. Chan, C. Glackin, et al. (2005)
Cancer Res. 65, 5153-5162
   Abstract »    Full Text »    PDF »
A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome.
H. Guenou, K. Kaabeche, S. L. Mee, and P. J. Marie (2005)
Hum. Mol. Genet. 14, 1429-1439
   Abstract »    Full Text »    PDF »
Myocyte Enhancer Factor 2 Acetylation by p300 Enhances Its DNA Binding Activity, Transcriptional Activity, and Myogenic Differentiation.
K. Ma, J. K. L. Chan, G. Zhu, and Z. Wu (2005)
Mol. Cell. Biol. 25, 3575-3582
   Abstract »    Full Text »    PDF »
Sharp-1/DEC2 Inhibits Skeletal Muscle Differentiation through Repression of Myogenic Transcription Factors.
S. Azmi, A. Ozog, and R. Taneja (2004)
J. Biol. Chem. 279, 52643-52652
   Abstract »    Full Text »    PDF »
Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors.
T.-g. Kim, J. Chen, J. Sadoshima, and Y. Lee (2004)
Mol. Cell. Biol. 24, 10151-10160
   Abstract »    Full Text »    PDF »
Paraxis Is a Basic Helix-Loop-Helix Protein That Positively Regulates Transcription through Binding to Specific E-box Elements.
J. Wilson-Rawls, J. M. Rhee, and A. Rawls (2004)
J. Biol. Chem. 279, 37685-37692
   Abstract »    Full Text »    PDF »
A Mouse Model of Uterine Leiomyosarcoma.
K. Politi, M. Szabolcs, P. Fisher, A. Kljuic, T. Ludwig, and A. Efstratiadis (2004)
Am. J. Pathol. 164, 325-336
   Abstract »    Full Text »    PDF »
Twist2, a novel ADD1/SREBP1c interacting protein, represses the transcriptional activity of ADD1/SREBP1c.
Y. S. Lee, H. H. Lee, J. Park, E. J. Yoo, C. A. Glackin, Y. I. Choi, S. H. Jeon, R. H. Seong, S. D. Park, and J. B. Kim (2003)
Nucleic Acids Res. 31, 7165-7174
   Abstract »    Full Text »    PDF »
The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites.
B. S. Mankoo, S. Skuntz, I. Harrigan, E. Grigorieva, A. Candia, C. V. E. Wright, H. Arnheiter, and V. Pachnis (2003)
Development 130, 4655-4664
   Abstract »    Full Text »    PDF »
Twist Is Up-Regulated in Response to Wnt1 and Inhibits Mouse Mammary Cell Differentiation.
L. R. Howe, O. Watanabe, J. Leonard, and A. M. C. Brown (2003)
Cancer Res. 63, 1906-1913
   Abstract »    Full Text »    PDF »
Basic Helix-Loop-Helix Transcription Factor Epicardin/Capsulin/Pod-1 Suppresses Differentiation by Negative Regulation of Transcription.
N. Funato, K. Ohyama, T. Kuroda, and M. Nakamura (2003)
J. Biol. Chem. 278, 7486-7493
   Abstract »    Full Text »    PDF »
Dermo-1, a Multifunctional Basic Helix-Loop-Helix Protein, Represses MyoD Transactivation via the HLH Domain, MEF2 Interaction, and Chromatin Deacetylation.
X. Q. Gong and L. Li (2002)
J. Biol. Chem. 277, 12310-12317
   Abstract »    Full Text »    PDF »
Characterization of a dominant negative C. elegans Twist mutant protein with implications for human Saethre-Chotzen syndrome.
A. K. Corsi, T. M. Brodigan, E. M. Jorgensen, and M. Krause (2002)
Development 129, 2761-2772
   Abstract »    Full Text »    PDF »
The Transcriptional Repressor ZEB Regulates p73 Expression at the Crossroad between Proliferation and Differentiation.
G. Fontemaggi, A. Gurtner, S. Strano, Y. Higashi, A. Sacchi, G. Piaggio, and G. Blandino (2001)
Mol. Cell. Biol. 21, 8461-8470
   Abstract »    Full Text »    PDF »
Common Regulation of Growth Arrest and Differentiation of Osteoblasts by Helix-Loop-Helix Factors.
N. Funato, K. Ohtani, K. Ohyama, T. Kuroda, and M. Nakamura (2001)
Mol. Cell. Biol. 21, 7416-7428
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans twist plays an essential role in non-striated muscle development.
A. K. Corsi, S. A. Kostas, A. Fire, and M. Krause (2000)
Development 127, 2041-2051
   Abstract »    PDF »
The steroid receptor coactivator, GRIP-1, is necessary for MEF-2C-dependent gene expression and skeletal muscle differentiation.
S. L. Chen, D. H. Dowhan, B. M. Hosking, and G. E.O. Muscat (2000)
Genes & Dev. 14, 1209-1228
   Abstract »    Full Text »
Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location.
V. El Ghouzzi, L. Legeai-Mallet, S. Aresta, C. Benoist, A. Munnich, J. d. Gunzburg, and J. Bonaventure (2000)
Hum. Mol. Genet. 9, 813-819
   Abstract »    Full Text »    PDF »
Cloning and Characterization of a Novel Kruppel-associated Box Family Transcriptional Repressor That Interacts with the Retinoblastoma Gene Product, RB.
S. X. Skapek, D. Jansen, T.-F. Wei, T. McDermott, W. Huang, E. N. Olson, and E. Y.-H. P. Lee (2000)
J. Biol. Chem. 275, 7212-7223
   Abstract »    Full Text »    PDF »
OUT, a Novel Basic Helix-Loop-Helix Transcription Factor with an Id-like Inhibitory Activity.
O. Narumi, S. Mori, S. Boku, Y. Tsuji, N. Hashimoto, S.-I. Nishikawa, and Y. Yokota (2000)
J. Biol. Chem. 275, 3510-3521
   Abstract »    Full Text »    PDF »
Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms.
M. E. Massari and C. Murre (2000)
Mol. Cell. Biol. 20, 429-440
   Full Text »
Hes6 acts in a positive feedback loop with the neurogenins to promote neuronal differentiation.
N Koyano-Nakagawa, J Kim, D Anderson, and C Kintner (2000)
Development 127, 4203-4216
   Abstract »    PDF »
Independent Repressor Domains in ZEB Regulate Muscle and T-Cell Differentiation.
A. A. Postigo and D. C. Dean (1999)
Mol. Cell. Biol. 19, 7961-7971
   Abstract »    Full Text »    PDF »
Bridge-1, a Novel PDZ-Domain Coactivator of E2A-Mediated Regulation of Insulin Gene Transcription.
M. K. Thomas, K.-M. Yao, M. S. Tenser, G. G. Wong, and J. F. Habener (1999)
Mol. Cell. Biol. 19, 8492-8504
   Abstract »    Full Text »    PDF »
twist is a potential oncogene that inhibits apoptosis.
R. Maestro, A. P. D. Tos, Y. Hamamori, S. Krasnokutsky, V. Sartorelli, L. Kedes, C. Doglioni, D. H. Beach, and G. J. Hannon (1999)
Genes & Dev. 13, 2207-2217
   Abstract »    Full Text »
MyoR: A muscle-restricted basic helix-loop-helix transcription factor that antagonizes the actions of MyoD.
J. Lu, R. Webb, J. A. Richardson, and E. N. Olson (1999)
PNAS 96, 552-557
   Abstract »    Full Text »    PDF »
Molecular Consequences of Ds Insertion Into and Excision From the Helix-Loop-Helix Domain of the Maize R Gene.
Y. Liu, L. Wang, J. L. Kermicle, and S. R. Wessler (1998)
Genetics 150, 1639-1648
   Abstract »    Full Text »
Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning.
B. D. Harfe, A. V. Gomes, C. Kenyon, J. Liu, M. Krause, and A. Fire (1998)
Genes & Dev. 12, 2623-2635
   Abstract »    Full Text »
Understanding Adipocyte Differentiation.
F. M. GREGOIRE, C. M. SMAS, and H. S. SUL (1998)
Physiol Rev 78, 783-809
   Abstract »    Full Text »    PDF »
The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis.
R. M. Cripps, B. L. Black, B. Zhao, C.-L. Lien, R. A. Schulz, and E. N. Olson (1998)
Genes & Dev. 12, 422-434
   Abstract »    Full Text »
MEF2B Is a Component of a Smooth Muscle-specific Complex That Binds an A/T-rich Element Important for Smooth Muscle Myosin Heavy Chain Gene Expression.
Y. Katoh, J. D. Molkentin, V. Dave, E. N. Olson, and M. Periasamy (1998)
J. Biol. Chem. 273, 1511-1518
   Abstract »    Full Text »    PDF »
Twist and Notch negatively regulate adult muscle differentiation in Drosophila.
S Anant, S Roy, and K VijayRaghavan (1998)
Development 125, 1361-1369
   Abstract »    PDF »
A Dominant-Negative Form of Transcription Factor MEF2 Inhibits Myogenesis.
O. I. Ornatsky, J. J. Andreucci, and J. C. McDermott (1997)
J. Biol. Chem. 272, 33271-33278
   Abstract »    Full Text »    PDF »
Differential Interactions of Id Proteins with Basic-Helix-Loop-Helix Transcription Factors.
K. Langlands, X. Yin, G. Anand, and E. V. Prochownik (1997)
J. Biol. Chem. 272, 19785-19793
   Abstract »    Full Text »    PDF »
Cloning and Functional Characterization of Roaz, a Zinc Finger Protein that Interacts with O/E-1 to Regulate Gene Expression: Implications for Olfactory Neuronal Development.
R. Y. L. Tsai and R. R. Reed (1997)
J. Neurosci. 17, 4159-4169
   Abstract »    Full Text »    PDF »
Characterization of the Promoter of SF-1, an Orphan Nuclear Receptor Required for Adrenal and Gonadal Development.
K. G. Woodson, P. A. Crawford, Y. Sadovsky, and J. Milbrandt (1997)
Mol. Endocrinol. 11, 117-126
   Abstract »    Full Text »
Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development.
Z Yin, X. Xu, and M Frasch (1997)
Development 124, 4971-4982
   Abstract »    PDF »
Emergence of determined myotome precursor cells in the somite.
B. Williams and C. Ordahl (1997)
Development 124, 4983-4997
   Abstract »    PDF »
Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo.
R Maeda, A Kobayashi, R Sekine, J. Lin, H Kung, and M Maeno (1997)
Development 124, 2553-2560
   Abstract »    PDF »
Analysis of the Inhibition of MyoD Activity by ITF-2B and Full-length E12/E47.
H. Petropoulos and I. S. Skerjanc (2000)
J. Biol. Chem. 275, 25095-25101
   Abstract »    Full Text »    PDF »
Regulation of Myogenic Terminal Differentiation by the Hairy-related Transcription Factor CHF2.
J. Sun, C. N. Kamei, M. D. Layne, M. K. Jain, J. K. Liao, M.-E. Lee, and M. T. Chin (2001)
J. Biol. Chem. 276, 18591-18596
   Abstract »    Full Text »    PDF »
Insulin-like Growth Factor 1 (IGF-1)-induced Twist Expression Is Involved in the Anti-apoptotic Effects of the IGF-1 Receptor.
J. Dupont, A. M. Fernandez, C. A. Glackin, L. Helman, and D. LeRoith (2001)
J. Biol. Chem. 276, 26699-26707
   Abstract »    Full Text »    PDF »
HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program.
X. Gao, T. Chandra, M.-O. Gratton, I. Quelo, J. Prud'homme, S. Stifani, and R. St-Arnaud (2001)
J. Cell Biol. 154, 1161-1172
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)