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PMID: 8455629 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors.

Molecular and cellular biology ·Vol. 13 ·No. 4 ·1993-04-00 ·Pages 2564-77

McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B

Abstract

The myocyte enhancer-binding factor 2 (MEF2) site is an essential element of many muscle-specific enhancers and promoters that binds nuclear proteins from muscle and brain. Recently, we have cloned a family of MEF2 transcription factors produced by two genes that, at the mRNA level, are broadly expressed and produce tissue-specific isoforms by posttranscriptional processes (Y.-T. Yu, R. E. Breitbart, L. B. Smoot, Y. Lee, V. Mahdavi, and B. Nadal-Ginard, Genes Dev. 6:1783-1798, 1992). Here, we report the isolation and functional characterization of cDNA clones encoding four MEF2 factors derived from a separate gene that we have named hMEF2C. In contrast to those of the previously reported genes, the transcripts of the hMEF2C gene are restricted to skeletal muscle and brain. One of the alternate exons is exclusively present in brain transcripts. The products of this gene have DNA-binding and trans-activating activities indistinguishable from those of the previously reported MEF2 factors. The hMEF2C gene is induced late during myogenic differentiation, and its expression is limited to a subset of cortical neurons. The potential targets for this transcription factor in a subset of neurons are not known at this time. The strict tissue-specific pattern of expression of hMEF2C in comparison with the more ubiquitous expression of other MEF2 genes suggests a different mode of regulation and a potentially important role of hMEF2C factors in myogenesis and neurogenesis.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence Brain/physiology Cells, Cultured Cloning, Molecular Consensus Sequence DNA-Binding Proteins/genetics Gene Expression Genes Humans Immunologic Techniques In Vitro Techniques MEF2 Transcription Factors Mice Molecular Sequence Data Muscles/physiology Myogenic Regulatory Factors Neurons/physiology Oligodeoxyribonucleotides/chemistry Polymerase Chain Reaction RNA, Messenger/genetics Sequence Alignment Tissue Distribution Transcription Factors/genetics Transcription, Genetic
Chemicals
DNA-Binding Proteins MEF2 Transcription Factors Myogenic Regulatory Factors Oligodeoxyribonucleotides RNA, Messenger Transcription Factors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
McDermott J C
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts.
Cardoso M C
Yu Y T
Andres V
Leifer D
Krainc D
Lipton S A
Nadal-Ginard B
References (51)
51 references, click to expand
  1. Promoter specificity of basal transcription factors.
    Cell. 1992 Mar 20;68(6):1135-44 PMID: 1547507
  2. Genetic Control of Flower Development by Homeotic Genes in Antirrhinum majus.
    Science. 1990 Nov 16;250(4983):931-6 PMID: 17746916
  3. Alternative splicing in the control of gene expression.
    Annu Rev Genet. 1989;23:527-77 PMID: 2694943
  4. 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
  5. 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
  6. 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
  7. The protein encoded by the Arabidopsis homeotic gene agamous resembles transcription factors.
    Nature. 1990 Jul 5;346(6279):35-9 PMID: 1973265
  8. 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
  9. A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer.
    Cell. 1992 Jan 10;68(1):133-42 PMID: 1732062
  10. A dominant negative form of transcription activator mTFE3 created by differential splicing.
    Science. 1991 Oct 4;254(5028):94-7 PMID: 1840705
  11. 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
  12. 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
  13. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs.
    Mol Cell Biol. 1989 Mar;9(3):946-58 PMID: 2657393
  14. Transgenic mouse eggs with functional hamster sperm receptors in their zona pellucida.
    Development. 1992 Aug;115(4):937-46 PMID: 1333402
  15. More is better: activators and repressors from the same gene.
    Cell. 1992 Feb 7;68(3):411-4 PMID: 1739963
  16. 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
  17. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter.
    Cell. 1989 Feb 24;56(4):563-72 PMID: 2492906
  18. Positive and negative regulatory DNA elements including a CCArGG box are involved in the cell type-specific expression of the human muscle dystrophin gene.
    J Biol Chem. 1992 May 25;267(15):10823-30 PMID: 1316911
  19. 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
  20. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins.
    J Mol Biol. 1978 Mar 25;120(1):97-120 PMID: 642007
  21. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain.
    Cell. 1989 Aug 25;58(4):741-53 PMID: 2504497
  22. MyoD family: a paradigm for development?
    Genes Dev. 1990 Sep;4(9):1454-61 PMID: 2253873
  23. 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
  24. 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
  25. Characterization of a promoter element required for transcription in myocardial cells.
    J Biol Chem. 1991 Feb 15;266(5):3309-16 PMID: 1993702
  26. The sarcomeric actin CArG-binding factor is indistinguishable from the c-fos serum response factor.
    Mol Cell Biol. 1989 Feb;9(2):515-22 PMID: 2710114
  27. The myoD gene family: nodal point during specification of the muscle cell lineage.
    Science. 1991 Feb 15;251(4995):761-6 PMID: 1846704
  28. Multiple positive and negative 5' regulatory elements control the cell-type-specific expression of the embryonic skeletal myosin heavy-chain gene.
    Mol Cell Biol. 1987 Dec;7(12):4377-89 PMID: 2830491
  29. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  30. M-CAT binding factor, a novel trans-acting factor governing muscle-specific transcription.
    Mol Cell Biol. 1990 Aug;10(8):4271-83 PMID: 2370866
  31. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif.
    Cell. 1988 Dec 2;55(5):887-98 PMID: 3142690
  32. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes.
    Annu Rev Biochem. 1987;56:467-95 PMID: 3304142
  33. 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
  34. The MADS box gene family in tomato: temporal expression during floral development, conserved secondary structures and homology with homeotic genes from Antirrhinum and Arabidopsis.
    Plant J. 1991 Sep;1(2):255-66 PMID: 1688249
  35. 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
  36. 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
  37. Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro.
    J Cell Biol. 1982 Dec;95(3):763-70 PMID: 6185504
  38. Transcriptional control signals of a eukaryotic protein-coding gene.
    Science. 1982 Jul 23;217(4557):316-24 PMID: 6283634
  39. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  40. Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis.
    Nature. 1989 Sep 28;341(6240):303-7 PMID: 2552320
  41. The homeotic gene APETALA3 of Arabidopsis thaliana encodes a MADS box and is expressed in petals and stamens.
    Cell. 1992 Feb 21;68(4):683-97 PMID: 1346756
  42. Expression of a single transfected cDNA converts fibroblasts to myoblasts.
    Cell. 1987 Dec 24;51(6):987-1000 PMID: 3690668
  43. 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
  44. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  45. Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products.
    EMBO J. 1989 Dec 1;8(12):3617-25 PMID: 2583111
  46. 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
  47. A MyoD1-independent muscle-specific enhancer controls the expression of the beta-myosin heavy chain gene in skeletal and cardiac muscle cells.
    J Biol Chem. 1991 Nov 25;266(33):22678-88 PMID: 1939278
  48. AGL1-AGL6, an Arabidopsis gene family with similarity to floral homeotic and transcription factor genes.
    Genes Dev. 1991 Mar;5(3):484-95 PMID: 1672119
  49. The SV40 72 base repair repeat has a striking effect on gene expression both in SV40 and other chimeric recombinants.
    Nucleic Acids Res. 1981 Nov 25;9(22):6047-68 PMID: 6273820
  50. Human SRF-related proteins: DNA-binding properties and potential regulatory targets.
    Genes Dev. 1991 Dec;5(12A):2327-41 PMID: 1748287
  51. The war of the whorls: genetic interactions controlling flower development.
    Nature. 1991 Sep 5;353(6339):31-7 PMID: 1715520
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1993-04-00
Pages
2564-77
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359588
Subset
IM
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