Abstract
MEF-2 is a muscle-specific DNA binding activity that recognizes an A+T-rich sequence found in the control regions of numerous muscle-specific genes. The recent cloning of MEF-2 showed that it belongs to the MADS (MCM1, Agamous, Deficiens, and serum-response factor) box family of transcription factors and that MEF-2 mRNA is expressed ubiquitously. Here we describe the cloning of a member of the MEF-2 gene family, referred to as MEF-2C, that is nearly identical to other MEF-2 gene products in the MADS box but diverges from other members of the family outside of this domain. MEF-2C binds the MEF-2 site with high affinity and can activate transcription of a reporter gene linked to tandem copies of that site. In contrast to previously described members of the MEF-2 family, MEF-2C transcripts are highly enriched in skeletal muscle, spleen, and brain of adult mice and are upregulated during myoblast differentiation. These results suggest that the MEF-2 site is a target for a diverse family of proteins that regulates transcription in a variety of cell types.
MeSH Terms
Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Brain/metabolism
Cell Line
Cloning, Molecular
Creatine Kinase/metabolism
DNA/genetics,isolation & purification
DNA-Binding Proteins/genetics,metabolism
Exons
Humans
MADS Domain Proteins
MEF2 Transcription Factors
Mice
Molecular Sequence Data
Multigene Family
Muscles/metabolism
Myocardium/metabolism
Myogenic Regulatory Factors
Oligodeoxyribonucleotides
Organ Specificity
Polymerase Chain Reaction
Protein Biosynthesis
RNA, Messenger/metabolism
Restriction Mapping
Sequence Homology, Amino Acid
Spleen/metabolism
Transcription Factors/genetics,metabolism
Transcription, Genetic
Transfection
Chemicals
DNA-Binding Proteins
MADS Domain Proteins
MEF2 Transcription Factors
MEF2C protein, human
Mef2c protein, mouse
Myogenic Regulatory Factors
Oligodeoxyribonucleotides
RNA, Messenger
Transcription Factors
DNA
Creatine Kinase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Martin J F
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Schwarz J J
Olson E N
References (29)
29 references, click to expand
-
Genetic Control of Flower Development by Homeotic Genes in Antirrhinum majus.
Science. 1990 Nov 16;250(4983):931-6
PMID: 17746916
-
A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells.
Mol Cell Biol. 1992 Oct;12(10):4384-90
PMID: 1328854
-
The human skeletal alpha-actin gene is regulated by a muscle-specific enhancer that binds three nuclear factors.
Gene Expr. 1992;2(2):111-26
PMID: 1633435
-
Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor.
Science. 1992 Aug 21;257(5073):1089-95
PMID: 1509260
-
The protein encoded by the Arabidopsis homeotic gene agamous resembles transcription factors.
Nature. 1990 Jul 5;346(6279):35-9
PMID: 1973265
-
Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene.
Mol Cell Biol. 1989 Jun;9(6):2627-40
PMID: 2761542
-
Analysis of the myogenin promoter reveals an indirect pathway for positive autoregulation mediated by the muscle-specific enhancer factor MEF-2.
Mol Cell Biol. 1992 Sep;12(9):3665-77
PMID: 1324403
-
Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element.
Cell. 1992 Feb 7;68(3):597-612
PMID: 1339307
-
A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program.
Genes Dev. 1989 May;3(5):628-40
PMID: 2473006
-
Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo.
Cell. 1991 Jul 26;66(2):305-15
PMID: 1649701
-
Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element.
Cell. 1988 Dec 23;55(6):989-1003
PMID: 3203386
-
Brain and muscle creatine kinase genes contain common TA-rich recognition protein-binding regulatory elements.
Mol Cell Biol. 1990 Sep;10(9):4826-36
PMID: 2388627
-
Helix-loop-helix proteins as regulators of muscle-specific transcription.
J Biol Chem. 1993 Jan 15;268(2):755-8
PMID: 8380414
-
Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells.
J Mol Biol. 1988 Dec 5;204(3):593-606
PMID: 3066908
-
Characterization of a promoter element required for transcription in myocardial cells.
J Biol Chem. 1991 Feb 15;266(5):3309-16
PMID: 1993702
-
Promoter upstream elements of the chicken cardiac myosin light-chain 2-A gene interact with trans-acting regulatory factors for muscle-specific transcription.
Mol Cell Biol. 1989 Jun;9(6):2513-25
PMID: 2761538
-
Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products.
Mol Cell Biol. 1991 Oct;11(10):4854-62
PMID: 1656214
-
A protein domain conserved between yeast MCM1 and human SRF directs ternary complex formation.
EMBO J. 1991 Dec;10(13):4219-29
PMID: 1756729
-
Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors.
Genes Dev. 1992 Sep;6(9):1783-98
PMID: 1516833
-
Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF.
Nature. 1991 Dec 19-26;354(6354):531-4
PMID: 1722028
-
Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis.
EMBO J. 1992 Dec;11(13):4981-91
PMID: 1281451
-
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
Nucleic Acids Res. 1987 Oct 26;15(20):8125-48
PMID: 3313277
-
Characterization of two new genes essential for vegetative growth in Saccharomyces cerevisiae: nucleotide sequence determination and chromosome mapping.
Gene. 1987;55(2-3):265-75
PMID: 3311883
-
Identification of a novel TA-rich DNA binding protein that recognizes a TATA sequence within the brain creatine kinase promoter.
Nucleic Acids Res. 1988 Sep 26;16(18):8925-44
PMID: 3174436
-
A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes.
Mol Cell Biol. 1989 Nov;9(11):5022-33
PMID: 2601707
-
A conserved 28-base-pair element (HF-1) in the rat cardiac myosin light-chain-2 gene confers cardiac-specific and alpha-adrenergic-inducible expression in cultured neonatal rat myocardial cells.
Mol Cell Biol. 1991 Apr;11(4):2273-81
PMID: 1848675
-
Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization.
Genes Dev. 1990 Apr;4(4):582-95
PMID: 2163343
-
Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene.
Mol Cell Biol. 1988 Jul;8(7):2896-909
PMID: 3405222
-
Human SRF-related proteins: DNA-binding properties and potential regulatory targets.
Genes Dev. 1991 Dec;5(12A):2327-41
PMID: 1748287