Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromatin structure of the 3' end of the human apolipoprotein B gene has been examined. Two DNaseI hypersensitive sites were present in nuclei from liver-derived HepG2 cells and intestine-derived CaCo-2 cells, in which the apo-B gene is transcriptionally active, but were absent from HeLa cells, where the gene is not expressed, and from free DNA. The region in a segment enriched in recognition sites for topoisomerase II and known to participate in anchoring the 3' end of the gene to the nuclear matrix. The second DNaseI hypersensitive site resided in the 3' untranslated portion of the gene. Furthermore, nucleosomes were present along a 1.4-kilobase (HindIII-BamHI) segment of DNA containing the two 3' DNaseI hypersensitive sites, and a static array of nucleosomes was present along the A/T-rich hypervariable region.
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PMID:DNaseI hypersensitive sites at the 3' end of the human apolipoprotein B gene. 216 68

In eukaryotic cells, chromatin is organized as domains or loops that are generated by periodic attachment of the chromatin fiber to protein components of a nuclear matrix, or scaffold. These chromosomal loops may have a function in gene regulation. The length of the chromatin domain encompassing the human apolipoprotein B gene was studied by determining the locations of nuclear matrix attachment sites as well as the boundaries of the DNase I-sensitive domain in cells that express the gene (such as HepG2 and CaCo-2 cells) and in those that do not (HeLa cells). Three nuclear matrix attachment regions (MARs) of the human apolipoprotein B gene have been localized: a 3' -proximal MAR, between nucleotides +43,186 and +43,850; a 5' -proximal MAR, between nucleotides -2,765 and -1,801; and a 5' -distal MAR, between nucleotides -5,262 and -4,048. Both the 3' -proximal and the 5' -distal MARS were present in cells that express the gene (HepG2 and CaCo-2 cells) as well as in cells that do not (HeLa cells), whereas the 5' -proximal MAR was detected only in HepG2 cells. These MARs were located at the bases of chromosomal loops in histone-extracted nuclei in all three cell lines. Various classes of A/T-rich sequences resembling the recognition site for topoisomerase II were present within the MAR-containing fragments. The boundaries of the DNase I-sensitive domain coincide with the positions of the 3' -proximal and 5' -distal matrix attachment sites. These results suggest the existence of a 47.5-kilobase domain that represents a topologically sequestered functional unit containing the coding region and all known cis-acting regulatory elements of the human apolipoprotein B gene.
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PMID:The limits of the DNase I-sensitive domain of the human apolipoprotein B gene coincide with the locations of chromosomal anchorage loops and define the 5' and 3' boundaries of the gene. 259 70

The internal structure of different alleles of the minisatellite present at the 3' end of the apolipoprotein B (ApoB) gene has been analysed by different approaches including sequencing. The repeat unit arrangements of the minisatellite on 570 chromosomes belonging to European and African populations were thus determined. It was possible to group the alleles using this structural criterion much more clearly than by the number of repeat units which can in some cases be misleading in case-control genetic epidemiological studies using such DNA sequences as markers. We were thus able to define five types (a to e) of alleles and their subtypes and to recognize clearly those which are, respectively, specific of the African and Caucasian populations. A phylogeny of the different alleles found in all human populations could also be deduced by this approach. The different putative mutational events leading from one type, or subtype, to the other were simply determined as point mutations, expansion/contraction and conversion events. Sequencing of one chimpanzee's allele suggested that the ApoB minisatellite was present before divergence between great apes and humans. It was determined also that a particular ApoB gene haplotype was in linkage disequilibrium with the minisatellite (a) type of alleles. This and the observation that the potential scaffold attachment regions (SAR) and topoisomerase II binding sites present in this minisatellite have a different distribution between the Caucasian and the African specific alleles suggest that the minisatellite could be involved in the epidemiology of coronary diseases.
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PMID:Structural analysis of the minisatellite present at the 3' end of the human apolipoprotein B gene: new definition of the alleles and evolutionary implications. 878 40