The basic helix-loop-helix protein upstream stimulating factor regulates the cardiac ventricular myosin light-chain 2 gene via independent cis regulatory elements

Previous studies have documented that 250 bp of the rat cardiac ventricular myosin light-chain 2 (MLC-2v) promoter is sufficient to confer cardiac muscle-specific expression on a luciferase reporter gene in both transgenic mice and primary cultured neonatal rat myocardial cells. Utilizing ligation-mediated PCR to perform in vivo dimethyl sulfate footprinting, the present study has identified protein-DNA interaction within the position from -176 to -165. This region, identified as MLE1, contains a core sequence, CACGTG, which conforms to the consensus E-box site and is identical to the upstream stimulating factor (USF)-binding site of the adenovirus major late promoter. Transient assays of luciferase reporter genes containing point mutations of the site demonstrate the importance of this cis regulatory element in the transcriptional activation of this cardiac muscle gene in ventricular muscle cells. The protein complex that occupies this site is capable of binding to HF-1a and PRE B sites which are known to be required for cardiac muscle-specific expression of rat MLC-2v and alpha-myosin heavy-chain genes, respectively. This study provides direct evidence that USF, a member of the basic helix-loop-helix leucine zipper family, binds to MLE1, HF-1a, and PRE B sites and suggests that it is a component of protein complexes that may coordinately control the expression of MLC-2v and alpha-myosin heavy-chain genes. The current study also provides evidence that USF can positively and negatively regulate the MLC-2v gene via independent cis regulatory elements.

[1]  K. Chien,et al.  Heterokaryons of cardiac myocytes and fibroblasts reveal the lack of dominance of the cardiac muscle phenotype , 1994, Molecular and cellular biology.

[2]  N. Copeland,et al.  A Mef2 gene that generates a muscle-specific isoform via alternative mRNA splicing , 1994, Molecular and cellular biology.

[3]  T. Maity,et al.  Ubiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells. , 1994, Nucleic acids research.

[4]  K. Chien,et al.  Positive regulatory elements (HF-1a and HF-1b) and a novel negative regulatory element (HF-3) mediate ventricular muscle-specific expression of myosin light-chain 2-luciferase fusion genes in transgenic mice , 1994, Molecular and cellular biology.

[5]  M. Rudnicki,et al.  MyoD or Myf-5 is required for the formation of skeletal muscle , 1993, Cell.

[6]  J. Thorburn,et al.  Potential role of helix-loop-helix proteins in cardiac gene expression. , 1993, Circulation research.

[7]  K. Chien,et al.  Positional specification of ventricular myosin light chain 2 expression in the primitive murine heart tube. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Brogan,et al.  Expression of the alpha-myosin heavy chain gene in the heart is regulated in part by an E-box-dependent mechanism. , 1993, The Journal of biological chemistry.

[9]  V. Rotter,et al.  The helix-loop-helix containing transcription factor USF binds to and transactivates the promoter of the p53 tumor suppressor gene. , 1993, Nucleic acids research.

[10]  K. Chien,et al.  Transcriptional regulation during cardiac growth and development. , 1993, Annual review of physiology.

[11]  B. Nadal-Ginard,et al.  Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors. , 1992, Genes & development.

[12]  G. Brem,et al.  Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory programs for cardiac and skeletal muscle-specific expression of a single contractile protein gene. , 1992, The Journal of biological chemistry.

[13]  W. Rutter,et al.  Interaction cloning: identification of a helix-loop-helix zipper protein that interacts with c-Fos. , 1992, Science.

[14]  S. Orkin,et al.  In vivo footprinting of the human alpha-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction , 1992, Molecular and cellular biology.

[15]  B. Wold,et al.  Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart. , 1992, Development.

[16]  K. Chien,et al.  A ubiquitous factor (HF-1a) and a distinct muscle factor (HF-1b/MEF-2) form an E-box-independent pathway for cardiac muscle gene expression , 1992, Molecular and cellular biology.

[17]  H. Olsen,et al.  Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene , 1992, Molecular and cellular biology.

[18]  R. Kingston,et al.  HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors , 1992, Molecular and cellular biology.

[19]  R. Roeder,et al.  Identification of USF as the ubiquitous murine factor that binds to and stimulates transcription from the immunoglobulin lambda 2-chain promoter. , 1992, Nucleic acids research.

[20]  M. T. Kozlowski,et al.  Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers. , 1992, Gene expression.

[21]  C. Dang,et al.  Max: functional domains and interaction with c-Myc. , 1992, Genes & development.

[22]  C. Glass,et al.  RXRβ: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements , 1991, Cell.

[23]  C. Dang,et al.  The upstream stimulatory factor binds to and activates the promoter of the rat class I alcohol dehydrogenase gene. , 1991, The Journal of biological chemistry.

[24]  G. Prendergast,et al.  Association of Myn, the murine homolog of Max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation , 1991, Cell.

[25]  R. Eisenman,et al.  Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. , 1991, Science.

[26]  H. Weintraub,et al.  Sequence-specific DNA binding by the c-Myc protein. , 1990, Science.

[27]  R. Roeder,et al.  The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. , 1990, Genes & development.

[28]  W. Rutter,et al.  Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. , 1990, Genes & development.

[29]  T. Braun,et al.  Myf‐6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. , 1990, The EMBO journal.

[30]  L. Su,et al.  TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. , 1990, Genes & development.

[31]  B. Wold,et al.  In vivo footprinting of a muscle specific enhancer by ligation mediated PCR. , 1990, Science.

[32]  S. Rhodes,et al.  Identification of MRF4: a new member of the muscle regulatory factor gene family. , 1989, Genes & development.

[33]  A. Brasier,et al.  Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. , 1989, BioTechniques.

[34]  K. Chien,et al.  Structure, organization, and expression of the rat cardiac myosin light chain-2 gene. Identification of a 250-base pair fragment which confers cardiac-specific expression. , 1989, The Journal of biological chemistry.

[35]  E. Olson,et al.  A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. , 1989, Genes & development.

[36]  David Baltimore,et al.  A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins , 1989, Cell.

[37]  Victor K. Lin,et al.  Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD , 1989, Cell.

[38]  K. Chien,et al.  Terminally differentiated neonatal rat myocardial cells proliferate and maintain specific differentiated functions following expression of SV40 large T antigen. , 1988, The Journal of biological chemistry.

[39]  T. J. Baldwin,et al.  Isolation and characterization of the mouse acetylcholine receptor delta subunit gene: identification of a 148-bp cis-acting region that confers myotube-specific expression , 1988, The Journal of cell biology.

[40]  G. Spizz,et al.  Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene , 1988, Molecular and cellular biology.

[41]  S. Nordeen,et al.  Luciferase reporter gene vectors for analysis of promoters and enhancers. , 1988, BioTechniques.

[42]  J. Johnson,et al.  The muscle creatine kinase gene is regulated by multiple upstream elements, including a muscle-specific enhancer , 1988, Molecular and cellular biology.

[43]  H. Weintraub,et al.  Expression of a single transfected cDNA converts fibroblasts to myoblasts , 1987, Cell.

[44]  F. Pieper,et al.  Upstream regions of the hamster desmin and vimentin genes regulate expression during in vitro myogenesis. , 1987, The EMBO journal.

[45]  P. Sharp,et al.  The major late transcription factor binds to and activates the mouse metallothionein I promoter. , 1987, Genes & development.

[46]  P. Sharp,et al.  The adenovirus major late transcription factor activates the rat gamma-fibrinogen promoter. , 1987, Science.

[47]  H. Okayama,et al.  High-efficiency transformation of mammalian cells by plasmid DNA. , 1987, Molecular and cellular biology.

[48]  N. Rosenthal.  Identification of regulatory elements of cloned genes with functional assays. , 1987, Methods in enzymology.

[49]  L. Kedes,et al.  Upstream regions of the human cardiac actin gene that modulate its transcription in muscle cells: presence of an evolutionarily conserved repeated motif , 1986, Molecular and cellular biology.

[50]  Phillip A. Sharp,et al.  An RNA polymerase II transcription factor binds to an upstream element in the adenovirus major late promoter , 1985, Cell.

[51]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[52]  R. Roeder,et al.  Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region , 1985, Cell.

[53]  Y. Kan,et al.  In vivo protein-DNA interactions at the f8-globin gene locus , 2022 .

[54]  Mitsuaki,et al.  SRot Promoter: an Efficient and Versatile Mammalian cDNA Expression System Composed of the Simian Virus 40 Early Promoter and the R-U5 Segment of Human T-Cell Leukemia Virus Type 1 Long Terminal Repeat , 2022 .