Previous Article | Next Article 
Molecular and Cellular Biology, December 2001, p. 8490-8503, Vol. 21, No. 24
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.24.8490-8503.2001
Molecular Dissection of DNA Sequences and Factors
Involved in Slow Muscle-Specific Transcription
Soledad
Calvo,
Detlef
Vullhorst,
Pratap
Venepally,
Jun
Cheng,
Irina
Karavanova, and
Andres
Buonanno*
Section on Molecular Neurobiology, National
Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland 20892
Received 1 May 2001/Returned for modification 25 June 2001/Accepted 18 September 2001
Transcription is a major regulatory mechanism for the generation of
slow- and fast-twitch myofibers. We previously identified an upstream
region of the slow TnI gene (slow upstream regulatory element [SURE])
and an intronic region of the fast TnI gene (fast intronic regulatory
element [FIRE]) that are sufficient to direct fiber type-specific
transcription in transgenic mice. Here we demonstrate that the
downstream half of TnI SURE, containing E box, NFAT, MEF-2, and CACC
motifs, is sufficient to confer pan-skeletal muscle-specific expression
in transgenic mice. However, upstream regions of SURE and FIRE are
required for slow and fast fiber type specificity, respectively. By
adding back upstream SURE sequences to the pan-muscle-specific
enhancer, we delineated a 15-bp region necessary for slow muscle
specificity. Using this sequence in a yeast one-hybrid screen, we
isolated cDNAs for general transcription factor 3 (GTF3)/muscle TFII-I
repeat domain-containing protein 1 (MusTRD1). GTF3 is a multidomain
nuclear protein related to initiator element-binding transcription
factor TF II-I; the genes for both proteins are deleted in persons with
Williams-Beuren syndrome, who often manifest muscle weakness. Gel
retardation assays revealed that full-length GTF3, as well as its
carboxy-terminal half, specifically bind the bicoid-like
motif of SURE (GTTAATCCG). GTF3 expression is neither muscle
nor fiber type specific. Its levels are highest during a period of
fetal development that coincides with the emergence of specific fiber
types and transiently increases in regenerating muscles damaged by
bupivacaine. We further show that transcription from TnI SURE is
repressed by GTF3 when overexpressed in electroporated adult soleus
muscles. These results suggest a role for GTF3 as a regulator of slow
TnI expression during early stages of muscle development and suggest
how it could contribute to Williams-Beuren syndrome.
*
Corresponding author. Mailing address: Section on
Molecular Neurobiology, National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD 20892. Phone:
(301) 496-3298. Fax: (301) 496-9939. E-mail:
buonanno{at}helix.nih.gov.

Present address: Universidad de Castilla la Mancha, Facultad de
Medicina, Albacete 02071,
Spain.

Present address: National Center for Biotechnology Information,
NIH, Bethesda, MD
20894.
Molecular and Cellular Biology, December 2001, p. 8490-8503, Vol. 21, No. 24
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.24.8490-8503.2001
This article has been cited by other articles:
-
Tsika, R. W., Schramm, C., Simmer, G., Fitzsimons, D. P., Moss, R. L., Ji, J.
(2008). Overexpression of TEAD-1 in Transgenic Mouse Striated Muscles Produces a Slower Skeletal Muscle Contractile Phenotype. J. Biol. Chem.
283: 36154-36167
[Abstract]
[Full Text]
-
Lazebnik, M. B., Tussie-Luna, M. I., Roy, A. L.
(2008). Determination and Functional Analysis of the Consensus Binding Site for TFII-I Family Member BEN, Implicated in Williams-Beuren Syndrome. J. Biol. Chem.
283: 11078-11082
[Abstract]
[Full Text]
-
Rana, Z. A., Gundersen, K., Buonanno, A.
(2008). Activity-dependent repression of muscle genes by NFAT. Proc. Natl. Acad. Sci. USA
105: 5921-5926
[Abstract]
[Full Text]
-
Vullhorst, D., Buonanno, A.
(2005). Multiple GTF2I-like Repeats of General Transcription Factor 3 Exhibit DNA Binding Properties: EVIDENCE FOR A COMMON ORIGIN AS A SEQUENCE-SPECIFIC DNA INTERACTION MODULE. J. Biol. Chem.
280: 31722-31731
[Abstract]
[Full Text]
-
Allen, D. L., Weber, J. N., Sycuro, L. K., Leinwand, L. A.
(2005). Myocyte Enhancer Factor-2 and Serum Response Factor Binding Elements Regulate Fast Myosin Heavy Chain Transcription in Vivo. J. Biol. Chem.
280: 17126-17134
[Abstract]
[Full Text]
-
Rana, Z. A, Gundersen, K., Buonanno, A., Vullhorst, D.
(2005). Imaging transcription in vivo: distinct regulatory effects of fast and slow activity patterns on promoter elements from vertebrate troponin I isoform genes. J. Physiol.
562: 815-828
[Abstract]
[Full Text]
-
Cheng, G., Merriam, A. P., Gong, B., Leahy, P., Khanna, S., Porter, J. D.
(2004). Conserved and muscle-group-specific gene expression patterns shape postnatal development of the novel extraocular muscle phenotype. Physiol. Genomics
18: 184-195
[Abstract]
[Full Text]
-
Lee, H. H. C., Choi, R. C. Y., Ting, A. K. L., Siow, N. L., Jiang, J. X. S., Massoulie, J., Tsim, K. W. K.
(2004). Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ: DIFFERENTIAL EXPRESSION IN FAST AND SLOW TWITCH MUSCLE FIBERS IS DRIVEN BY DISTINCT PROMOTERS. J. Biol. Chem.
279: 27098-27107
[Abstract]
[Full Text]
-
Mas, J.-A., Garcia-Zaragoza, E., Cervera, M.
(2004). Two Functionally Identical Modular Enhancers in Drosophila Troponin T Gene Establish the Correct Protein Levels in Different Muscle Types. Mol. Biol. Cell
15: 1931-1945
[Abstract]
[Full Text]
-
Yang, P., Kupershmidt, S., Roden, D. M.
(2004). Cloning and initial characterization of the human cardiac sodium channel (SCN5A) promoter. Cardiovasc Res
61: 56-65
[Abstract]
[Full Text]
-
Nguyen, Q.-G. V., Buskin, J. N., Himeda, C. L., Shield, M. A., Hauschka, S. D.
(2003). Differences in the Function of Three Conserved E-boxes of the Muscle Creatine Kinase Gene in Cultured Myocytes and in Transgenic Mouse Skeletal and Cardiac Muscle. J. Biol. Chem.
278: 46494-46505
[Abstract]
[Full Text]
-
Tassabehji, M.
(2003). Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet
12: R229-237
[Abstract]
[Full Text]
-
Leary, S. C., Lyons, C. N., Rosenberger, A. G., Ballantyne, J. S., Stillman, J., Moyes, C. D.
(2003). Fiber-type differences in muscle mitochondrial profiles. Am. J. Physiol. Regul. Integr. Comp. Physiol.
285: R817-R826
[Abstract]
[Full Text]
-
Polly, P., Haddadi, L. M., Issa, L. L., Subramaniam, N., Palmer, S. J., Tay, E. S. E., Hardeman, E. C.
(2003). hMusTRD1{alpha}1 Represses MEF2 Activation of the Troponin I Slow Enhancer. J. Biol. Chem.
278: 36603-36610
[Abstract]
[Full Text]
-
Karasseva, N., Tsika, G., Ji, J., Zhang, A., Mao, X., Tsika, R.
(2003). Transcription Enhancer Factor 1 Binds Multiple Muscle MEF2 and A/T-Rich Elements during Fast-to-Slow Skeletal Muscle Fiber Type Transitions. Mol. Cell. Biol.
23: 5143-5164
[Abstract]
[Full Text]
-
Vullhorst, D., Buonanno, A.
(2003). Characterization of General Transcription Factor 3, a Transcription Factor Involved in Slow Muscle-specific Gene Expression. J. Biol. Chem.
278: 8370-8379
[Abstract]
[Full Text]