Search PubMed⌕ Search

PubMed · 8996791

Interfering contexts of regulatory sequence elements.

Abstract

MOTIVATION: Although one would normally expect a given regulatory element to perform best when it fully matches its consensus sequence, this is generally far from being the case. Usually, almost none of the actual sites fits the consensus exactly, and some of those that do fit do not perform well. The main reason for that is the very nature of the sequences and the messages (codes) they contain. Normally, any given stretch of the sequence with one or another regulatory site not only carries this regulatory message, but several more messages of various types as well. These messages overlap with the regulatory element in such a way that the letter (base) which actually appears in any given sequence position simultaneously belongs to one or more additional codes. Apart from numerous individual codes (sequence patterns) specific for a given species or gene, there are many different general (universal) sequence codes all interacting with one another. These are the classical triplet code, DNA shape code, chromatin code, gene splicing code, modulation code and many more, including those that have not yet been discovered. Examples of overlapping of different codes and their interaction are discussed, as well as the role of degeneracy of the codes and the sequence complexity as a function of code density.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E N Trifonov. 1996. Interfering contexts of regulatory sequence elements.. https://doi.org/10.1093/bioinformatics%2F12.5.423

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

miR-503-3p promotes epithelial-mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin.

Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial-mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3' untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.

Base Sequence↗

Dual variant of Epstein-Barr virus in Hodgkin/Reed-Sternberg cells: single-cell PCR study on latent membrane protein-1 gene.

Isolation of single cells permits analysis of DNA or RNA from individual cells among heterogeneous populations. This technique is particularly useful in the study of classical Hodgkin's lymphoma (cHL) due to the scarcity of H/RS tumor cells among large numbers of reactive leukocytes. In a previous study, we found a high frequency of dual LMP-1 variant (concurrent presence of deleted and nondeleted variants) in cHL from whole-tissue sections. For the present study, we applied a single-cell isolation technique to determine the LMP-1 oncogene variant in EBV-associated H/RS cells. Five cases of EBV-infected cHL, containing nondeleted (n=1), deleted (n=1) and dual infection (n=3) based on whole-tissue section analysis, were selected for study. Paraffin-embedded tissue sections were stained with antibody to LMP-1 and positively stained H/RS cells isolated using a semiautomated micromanipulator. Each isolated single cell was subjected to PCR for amplification of the LMP-1 gene flanking the 30 bp deletion region and Xho1 restriction site. Cases with either nondeleted variant or the deleted variant showed similar LMP-1 variant expression in isolated single H/RS cells. However, 1 of the 3 cases with dual variants showed only the deleted variant in H/RS cells. The other 2 cases showed mixed patterns of deleted, nondeleted and dual LMP-1 variants in isolated single H/RS cells. All cases showed loss of the Xho1 restriction site, with the exception of the case with nondeleted LMP-1. Results of single-H/RS cell analysis of the Xho1 restriction site concur with those of whole-tissue section amplification. A mixed pattern of LMP-1 variants was observed in isolated H/RS cells, and it is speculated that this is due to the accumulation of mutation and deletion events.

Base Sequence↗

Structural and evolutionary consequences of unpaired cysteines in trypsinogen.

Vertebrate trypsins usually contain six disulfide bonds but human trypsin 1 (PRSS1) contains only five and human trypsin 2 (PRSS2) contains only four. To elucidate possible evolutionary pathways leading to the loss of disulfide bonds, we have constructed mutants lacking one or two cysteines of four disulfide bonds (C22-C157, C127-C232, C136-C201, and C191-C220) in rat anionic trypsinogen and followed their expression in the periplasm of Escherichia coli. When both cysteines of any of the above-mentioned disulfide bonds were replaced by alanines we found, as expected, proteolytically active enzymes. In the case of C127-C232 (missing from both human trypsins) and C191-C220 both single mutants gave active enzymes although their yield was significantly reduced. In contrast, only one of the single mutants of disulfide bonds C22-C157 and C136-C201 (missing from human trypsin 2) was expressed in E. coli. In the case of these disulfide bonds, we obtained no expression when the solvent accessible molecular surface of the free cysteine residue was the smaller one, indicating that a buried unpaired cysteine was more deleterious than one on the surface of the molecule.

Base Sequence↗