PubMed Health⌕ Search

Biomedical subjects

M Mercola

Publications and source records attributed to M Mercola.

44 records · Page 3Linked to original sources
PubMed1988

Strong transcriptional activation of translocated c-myc genes occurs without a strong nearby enhancer or promoter.

We have studied the transcriptional activation of translocated c-myc genes in murine plasmacytomas in which the translocation juncture occurs within the first intron of c-myc and juxtaposes c-myc with the immunoglobulin C alpha gene segment. It has been widely suggested that a novel transcriptional enhancer element located near the C alpha gene segment might activate the translocated c-myc gene. We have carried out an extensive search for such an element and find no significant transcriptional enhancer activity in a 22 kb region encompassing the translocation junction, C alpha gene segment and regions 3' of C alpha. We also find that the cryptic promoter region of the translocated c-myc gene is a very weak promoter of transcription. Despite this evidence against the presence of strong transcriptional regulatory elements, the translocated c-myc gene locus is transcribed at high rates that are 25-greater than 100% of that measured for the highly active immunoglobulin genes in murine plasmacytomas. These data suggest the presence of a novel type of strong activator of transcription in the murine heavy chain locus.

Animals↗
PubMed1988

Growth factor superfamilies and mammalian embryogenesis.

With the availability of amino acid and nucleotide sequence information has come the realization that growth factors can be clustered in to superfamilies. Several of these superfamilies contain molecules that were not initially identified because of growth-promoting activities; rather they were discovered through their ability to regulate other processes. Certain members of these superfamilies are present during early mammalian embryogenesis. However, until recently, it has been difficult to manipulate the developing mammalian embryo to observe directly the effects of inappropriate, excessive, or reduced expression of these molecules. Despite this limitation, at least some of these molecules have been implicated in the control of differentiation and morphogenesis, two actions unpredicted from the cell biology of most of the growth factors. Moreover, these actions are reflected in nonmammalian species where homologues of the mammalian growth factors control crucial steps in the choice of developmental fate. This review describes five growth factor superfamilies and the role these molecules may have in controlling proliferation, differentiation, and morphogenesis during mammalian development.

Animals↗
PubMed1985

Immunoglobulin heavy-chain enhancer requires one or more tissue-specific factors.

Enhancer sequences are regulatory regions that greatly increase transcription of certain eukaryotic genes. An immunoglobulin heavy-chain variable gene segment is moved from a region lacking enhancer activity to a position adjacent to the known heavy-chain enhancer early in B-cell maturation. In lymphoid cells, the heavy-chain and SV40 enhancers bind a common factor essential for enhancer function. In contrast, fibroblast cells contain a functionally distinct factor that is used by the SV40 but not by the heavy-chain enhancer. The existence of different factors in these cells may explain the previously described lymphoid cell specificity of the heavy-chain enhancer.

Animals↗
PubMed1984

Translocation affects normal c-myc promoter usage and activates fifteen cryptic c-myc transcription starts in plasmacytoma M603.

Plasmacytoma M603 contains one normal, nontranslocated c-myc gene and one translocated c-myc gene in which c-myc exon 1 is juxtaposed with the immunoglobulin heavy chain enhancer and c-myc exons 2 and 3 are juxtaposed with C alpha. We find that steady-state c-myc RNA levels are 2-4 fold elevated in M603 relative to normal liver or spleen and that these transcripts originate predominantly if not exclusively from the translocated c-myc gene. Although both promoters on the nontranslocated c-myc gene are repressed, the proximal promoter, P1, is active on the translocated 5' c-myc region which is juxtaposed with the immunoglobulin heavy chain enhancer. The 3' portion of the translocated c-myc gene is transcribed from fifteen cryptic start sites and spliced at aberrant donor and acceptor splice sites, thereby generating a mixture of transcripts with different, abnormal 5' untranslated regions. Although the reason that translocation activates the cryptic c-myc starts in M603 is not completely understood, we show that truncation of the c-myc gene is not sufficient to activate cryptic transcription sites.

Animals↗
PubMed1983

Transcriptional enhancer elements in the mouse immunoglobulin heavy chain locus.

Two regions in the immunoglobulin heavy chain locus were tested for their ability to enhance transcription of the SV40 early promoter. A portion of the intervening sequence between the heavy chain joining region (Jh) and the constant region of the mu chain (Cmu) can enhance transcription when it is cloned either 5' or 3' to the SV40 early promoter. The region between C alpha and the alpha switch site, which occurs 5' to the translocated c-myc oncogene in many murine plasmacytomas, does not show transcriptional enhancer activity in this assay.

Animals↗
PubMed1980

The interaction of Cibacron Blue F3GA with troponin and its subunits.

Binding of troponin to Cibacron Blue F3GA-agarose column and its selective release from the gel in the presence of 0.5 M KCl provides the basis for a new purification method. The two-step procedure consists of isoelectric precipitation of tropomyosin and chromatography of the resultant crude troponin supernatant on Affi-Gel Blue column. Adsorption of troponin to the immobilized dye appears to occur through the troponin-T subunit. Troponin-I and troponin-C do not bind to the blue agarose column, whereas troponin-T binds to it very tightly. Binding of the dye to troponin-T prevents formation of troponin-T-troponin-C complex, but does not interfere with direct interaction of troponin-T with troponin-I. The activity of troponin in conferring calcium sensitivity on actomyosin ATPase is not affected by Cibacron Blue. Circular dichroism and difference absorption measurements of complexes of the blue dye with troponin and its subunits reveal the presence of a tight binding site on whole troponin and on troponin-T (KA greater than or equal to 10(6) M). The existence of weak binding sites for the dye on troponin and all of its subunits is deduced from difference absorption studies. Cibacron Blue appears to be a sensitive probe for subunit interactions in troponin.

Actins↗
PubMedDate not supplied

Spatially distinct head and heart inducers within the Xenopus organizer region.

BACKGROUND: The mouse anterior visceral endoderm, an extraembryonic tissue, expresses several genes essential for normal development of structures rostral to the anterior limit of the notochord and has been termed the head organizer. This tissue also has heart-inducing activity and expresses mCer1 which, like its Xenopus homolog cerberus, can induce markers of cardiac specification and anterior neural tissue when ectopically expressed. We investigated the relationship between head and heart induction in Xenopus embryos, which lack extraembryonic tissues. RESULTS: We found three regions of gene expression in the Xenopus organizer: deep endoderm, which expressed cerberus; prechordal mesoderm, which showed overlapping but non-identical expression of genes characteristic of the murine head organizer, such as XHex and XANF-1; and leading-edge dorsoanterior endoderm, which expressed both cerberus and a subset of the genes expressed by the prechordal mesoderm. Microsurgical ablation of the cerberus-expressing endoderm decreased the incidence of heart, but not head, formation. Removal of prechordal mesoderm, in contrast, caused deficits of anterior head structures. Finally, although misexpression of cerberus induced ectopic heads, it was unable to induce genes thought to participate in head induction. CONCLUSIONS: In Xenopus, the cerberus-expressing endoderm is required for heart, but not head, inducing activity. Therefore, this tissue is not the topological equivalent of the murine anterior visceral endoderm. We propose that, in Xenopus, cerberus is redundant to other bone morphogenetic protein (BMP) and Wnt antagonists located in prechordal mesoderm for head induction, but may be necessary for heart induction.

Animals↗