Imperial College London

DrPaulBarton

Faculty of MedicineNational Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7351 8140p.barton Website

 
 
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Location

 

2054Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

228 results found

Weydert A, Barton P, Harris AJ, Pinset C, Buckingham Met al., 1987, Developmental pattern of mouse skeletal myosin heavy chain gene transcripts in vivo and in vitro., Cell, Vol: 49, Pages: 121-129, ISSN: 0092-8674

We have studied the transcripts of the embryonic, perinatal, and adult fast myosin heavy chain (MHC) genes in mouse skeletal muscle in vivo before and after birth, and in vitro in myogenic cell lines. In vivo, in 15-day fetal muscle, embryonic and perinatal MHC mRNAs are both present, and the former is the major transcript. By 18 days the perinatal is predominant and the adult MHC mRNA appears. In beta-bungarotoxin-treated fetuses, a similar developmental pattern is detected, suggesting that it is nerve-independent and that primary myotubes alone undergo the same developmental changes. In vitro, in the absence of the nerve, embryonic, perinatal, and adult IIB MHC mRNAs accumulate. The level of the latter two isomRNAs is influenced by culture conditions.

Journal article

Barton PJ, Alonso S, Cohen A, Daubas P, Garner I, Robert B, Weydert A, Busckingham Met al., 1987, Actin and myosin gene expression in mouse striated muscle, Journal of Animal Science, Vol: 65, Pages: 157-167

Journal article

Buckingham M, Alonso S, Barton P, Cohen A, Daubas P, Garner I, Robert B, Weydert Aet al., 1986, Actin and myosin multigene families: their expression during the formation and maturation of striated muscle., Am J Med Genet, Vol: 25, Pages: 623-634, ISSN: 0148-7299

The initial formation of skeletal muscle fibers is accompanied by the expression of muscle-type actin and myosin genes. During subsequent maturation of muscle fibers in vivo, developmental changes in the fetal/adult isoforms of these proteins occur. Skeletal muscle-specific transcripts coding for different myosin heavy chains accumulate sequentially both in vivo and in vitro. A genetic analysis demonstrates that these genes are clustered, implicating cis-acting regulatory factors. In contrast, actin and myosin light chain genes are dispersed in the mouse genome. These gene families show a different developmental "strategy": Genes expressed in adult cardiac tissue are coexpressed with the corresponding skeletal muscle sequence during fetal development. This phenomenon also occurs in adult tissue. Under conditions of cardiac overload, adult rat hearts accumulate skeletal actin mRNA and cardiac actin transcripts. In some mouse lines, a mutant cardiac actin gene locus is present. The presence of a second active upstream promoter at this locus depresses transcription of the bone fide gene, resulting in low levels of mature cardiac actin mRNA. In this situation skeletal actin gene transcripts accumulate. Genes expressed in the same fetal or adult muscle phenotype are not linked, suggesting that their coexpression is regulated by transacting factors. The promoter regions of such genes in the mouse have no common characteristics of primary structure with the exception of an E1A-type enhancer core sequence, which has a conserved 5' flanking element, seen for actin and myosin light chain genes. Reintroduction of these promoter regions into muscle cells provides a functional test for such potential regulatory sequences.

Journal article

Garner I, Minty AJ, Alonso S, Barton PJ, Buckingham MEet al., 1986, A 5' duplication of the alpha-cardiac actin gene in BALB/c mice is associated with abnormal levels of alpha-cardiac and alpha-skeletal actin mRNAs in adult cardiac tissue., EMBO J, Vol: 5, Pages: 2559-2567, ISSN: 0261-4189

We describe the structure and transcriptional activity of the 5' portion of the alpha-cardiac actin gene of BALB/c mice. Southern blotting and DNA sequencing reveal that the promoter and first three exons of the gene are present as perfect repeats in a direct duplication of 9.5 kbp situated immediately upstream of the gene. Both promoters are active in adult cardiac tissue. Transcripts from the partial gene duplication give rise to novel RNAs that are spliced correctly in the actin region and polyadenylated. The level of mature alpha-cardiac actin mRNA is only 16.5% that found in mice that do not possess the duplication. This is due, at least in part, to interference at the transcriptional level. Transcripts from the alpha-skeletal actin gene accumulate to abnormally high levels in the hearts of such mutant mice. This result suggests tight regulatory coupling for this actin gene pair.

Journal article

Weydert A, Daubas P, Lazaridis I, Barton P, Garner I, Leader DP, Bonhomme F, Catalan J, Simon D, Guénet JLet al., 1985, Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene., Proc Natl Acad Sci U S A, Vol: 82, Pages: 7183-7187, ISSN: 0027-8424

Myosin heavy chain (MHC) genes are expressed as several distinct isoforms in a tissue- and stage-specific manner; three skeletal muscle MHC isoforms appear sequentially during development. We have isolated cDNA clones, identified by RNA blot hybridization and by nucleotide sequence determination as coding for portions of the embryonic (pMHC2.2), perinatal (pMHC16.2A), and alpha(V1) cardiac (pMHC141 and pMHC101) MHC isoforms. These four probes and the adult skeletal MHC probe (pMHC32) have been used on Southern blots of genomic DNA to detect restriction fragment length polymorphisms defining the alleles for these genes in mouse species Mus musculus and Mus spretus. In this way, we followed the segregation of skeletal and cardiac MHC genes in 42 offspring resulting from an interspecies backcross. We found that the embryonic, perinatal, and adult skeletal MHC genes are clustered on chromosome 11 near the locus nude, the skeletal and cardiac MHC genes do not cosegregate, and the alpha(V1) cardiac MHC gene is located on chromosome 14 close to Np-1. This result is in contrast to that for other contractile protein genes such as the alkali myosin light chain and the actin multigene families, which are dispersed in the genome.

Journal article

Robert B, Barton P, Minty A, Daubas P, Weydert A, Bonhomme F, Catalan J, Chazottes D, Guénet JL, Buckingham Met al., 1985, Investigation of genetic linkage between myosin and actin genes using an interspecific mouse back-cross., Nature, Vol: 314, Pages: 181-183, ISSN: 0028-0836

The introduction of cloned probes to follow the segregation of DNA restriction fragment length polymorphisms (RFLPs) has led to a revival of mendelian genetics in attempts to map the human genome. In the mouse, however, it has often proved difficult to detect an RFLP with a DNA probe between different inbred strains of the laboratory mouse. To circumvent this problem, we have used two species, Mus musculus domesticus and Mus spretus which interact as sympatric species but can be interbred under laboratory conditions. Because of the relative evolutionary distance between these species, they exhibit polymorphism at many more loci than do different strains of the usual M. m. domesticus laboratory mouse. This is also observed at the DNA level when the sizes of restriction fragments encoding a specific gene are compared. We have used these RFLPs between M. m. domesticus and M. spretus to follow the segregation of genes encoding different isoforms of myosin alkali light chains in the backcross progeny between these species and to compare this with that of other contractile protein genes. No linkage between these genes was observed.

Journal article

BARTON PJR, ROBERT B, FISZMAN MY, LEADER DP, BUCKINGHAM MEet al., 1985, THE SAME MYOSIN ALKALI LIGHT CHAIN GENE IS EXPRESSED IN ADULT CARDIAC ATRIA AND IN FETAL SKELETAL-MUSCLE, JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, Vol: 6, Pages: 461-475, ISSN: 0142-4319

Journal article

BARTON PJR, COHEN A, ROBERT B, FISZMAN MY, BONHOMME F, GUENET JL, LEADER DP, BUCKINGHAM MEet al., 1985, THE MYOSIN ALKALI LIGHT-CHAINS OF MOUSE VENTRICULAR AND SLOW SKELETAL-MUSCLE ARE INDISTINGUISHABLE AND ARE ENCODED BY THE SAME GENE, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 260, Pages: 8578-8584, ISSN: 0021-9258

Journal article

Buckingham M, Alonso S, Bugaisky G, Barton P, Cohen A, Daubas P, Minty A, Robert B, Weydert Aet al., 1985, The actin and myosin multigene families., Adv Exp Med Biol, Vol: 182, Pages: 333-344, ISSN: 0065-2598

Journal article

DAUBAS P, ALONSO S, BARTON P, COHEN A, GARNER I, ROBERT B, WEYDERT A, BUCKINGHAM Met al., 1985, GENE-EXPRESSION OF ACTINES AND MYOSINES DURING MYOGENESIS IN THE MOUSE, Publisher: MASSON EDITEUR, Pages: 252-252, ISSN: 0003-9594

Conference paper

BARTON PJR, BUCKINGHAM ME, 1985, THE MYOSIN ALKALI LIGHT CHAIN PROTEINS AND THEIR GENES, BIOCHEMICAL JOURNAL, Vol: 231, Pages: 249-261, ISSN: 0264-6021

Journal article

Buckingham M, Alonso S, Barton PJ, Bugaisky G, Cohen A, Daubas P, Minty A, Robert B, Weydert Aet al., 1984, Actin and myosin coding sequences in skeletal muscle development, Exp Biol Med, Vol: 9, Pages: 228-234

Journal article

BUCKINGHAM M, ALONSO S, BARTON P, BUGAISKY G, COHEN A, DAUBAS P, MINTY A, ROBERT B, WEYDERT Aet al., 1984, ACTIN AND MYOSIN MULTIGENE FAMILIES - THEIR EXPRESSION DURING SKELETAL-MUSCLE DIFFERENTIATION, BULLETIN DE L INSTITUT PASTEUR, Vol: 82, Pages: 67-73, ISSN: 0020-2452

Journal article

Malcolm S, Barton P, Murphy C, Ferguson-Smith MA, Bentley DL, Rabbitts THet al., 1982, Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization., Proc Natl Acad Sci U S A, Vol: 79, Pages: 4957-4961, ISSN: 0027-8424

The genes for human immunoglobulin kappa light chains have been localized in normal lymphocyte and fibroblast chromosomes by in situ hybridization of probes from cloned DNA fragments of the kappa variable region locus. The localization was achieved by counting grains (after autoradiography) over chromosomes in a number of karyotypes. The variable region gene probes hybridized in a cluster on a region of the chromosome 2 short arm close to the centromere (2cen leads to p12). This location was confirmed in lymphocytes from a balanced translocation carrier 46XXt (2; 16) (q13; q22). Our results show that human kappa light chain genes are located in the region of the break point observed in specific chromosomal translocations associated with Burkitt lymphoma.

Journal article

Barton P, Malcolm S, Murphy C, Ferguson-Smith MAet al., 1982, Localization of the human alpha-globin gene cluster to the short arm of chromosome 16 (16p12-16pter) by hybridization in situ., J Mol Biol, Vol: 156, Pages: 269-278, ISSN: 0022-2836

Journal article

MALCOLM S, BARTON P, FERGUSONSMITH MA, 1981, THE CHROMOSOMAL DISTRIBUTION OF REPETITIVE DNA-SEQUENCES WITHIN THE HUMAN BETA-GLOBIN GENE-CLUSTER, HUMAN GENETICS, Vol: 57, Pages: 388-393, ISSN: 0340-6717

Journal article

MALCOLM S, BARTON P, MURPHY C, FERGUSONSMITH MAet al., 1981, CHROMOSOMAL LOCALIZATION OF A SINGLE COPY GENE BY INSITU HYBRIDIZATION - HUMAN BETA-GLOBIN GENES ON THE SHORT ARM OF CHROMOSOME 11, ANNALS OF HUMAN GENETICS, Vol: 45, Pages: 135-141, ISSN: 0003-4800

Journal article

Malcolm S, Barton P, Tyler C, Ferguson-Smith MAet al., 1980, The use of restriction-enzyme fragments of cloned deoxyribonucleic acid for human globin-gene mapping [proceedings]., Biochem Soc Trans, Vol: 8, ISSN: 0300-5127

Journal article

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