Journal Article

Isochores and the Regulation of Gene Expression in the Human Genome

Stilianos Arhondakis, Fabio Auletta and Giorgio Bernardi

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 3, issue , pages 1080-1089
Published in print January 2011 |
Published online October 2011 | e-ISSN: 1759-6653 | DOI: https://dx.doi.org/10.1093/gbe/evr017

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It is well established that changes in the phenotype depend much more on changes in gene expression than on changes in protein-coding genes, and that cis-regulatory sequences and chromatin structure are two major factors influencing gene expression. Here, we investigated these factors at the genome-wide level by focusing on the trinucleotide patterns in the 0.1- to 25-kb regions flanking the human genes that are present in the GC-poorest L1 and GC-richest H3 isochore families, the other families exhibiting intermediate patterns. We could show 1) that the trinucleotide patterns of the 25-kb gene-flanking regions are representative of the very different patterns already reported for the whole isochores from the L1 and H3 families and, expectedly, identical in upstream and downstream locations; 2) that the patterns of the 0.1- to 0.5-kb regions in the L1 and H3 isochores are remarkably more divergent and more specific when compared with those of the 25-kb regions, as well as different in the upstream and downstream locations; and 3) that these patterns fade into the 25-kb patterns around 5kb in both upstream and downstream locations. The 25-kb findings indicate differences in nucleosome positioning and density in different isochore families, those of the 0.1- to 0.5-kb sequences indicate differences in the transcription factors that bind upstream and downstream of genes. These results indicate differences in the regulation of genes located in different isochore families, a point of functional and evolutionary relevance.

Keywords: dinucleotides; nucleosome positioning; promoters; trinucleotides

Journal Article.  4674 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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