Close encounters: RIDGEs, hyperacetylated chromatin, radiation breakpoints and genes differentially expressed in tumors cluster at specific human chromosome regions.
Through analysis of published data we positioned along human chromosome idiograms (850 bands) hyperacetylated H4 chromatin (H4(+a)), regions of increased gene expression (RIDGEs), antiRIDGEs, ionizing radiation breakpoints, integration sites of highly expressed GFP reporter constructs and candidate genes differentially expressed in tumor tissues. Highly expressed regions of the human genome (especially RIDGEs) seem to be more sensitive to radiation damage. Comparatively, antiRIDGEs appear as radiation resistant. Tumor deregulated genes tend to cluster along and in the neighborhood of RIDGEs. We detected 35 clusters of genes differentially expressed in tumor tissues which colocalize with RIDGEs; 23 of these clusters also exhibit radiation damage. RIDGEs also accumulate highly expressed GFP reporter construct integration sites, evolutionary breakpoints as well as amplicons and/or deletion-prone chromosome segments in tumors. This could indicate that abnormal gene (up- or down-) regulation might require high-throughput transcription nuclear micro-environments to occur. Our results suggest that the human genome is a combination of regions with marked disparities regarding the topology of increased gene expression, ionizing radiation damage, evolutionary breakpoints, integration sites, and abnormal gene regulation.
Folle
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GA
Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo 11600, Uruguay. folle@iibce.edu.uy
Liddle
P
P
Lafon-Hughes
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L
Di Tomaso
M V
MV
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008745:Methylation; D009369:Neoplasms / Q000235:genetics
D002843:Chromatin