|Public on Jun 04, 2013
|Genome-wide analysis of histone eviction by FAIRE-Seq
|Homo sapiens; Mus musculus
|Genome binding/occupancy profiling by high throughput sequencing
|A major class of chemotherapeutics targets topoisomerase II for DNA double-strand breaks and cancer cell elimination. We compare four members of this class?the anthracyclines doxorubicin, daunorubicin and aclarubicin that does not induce DNA breaks?and a different compound, etoposide. We define a novel activity for anthracyclines: histone eviction from open chromosomal areas. Since histone variant H2AX is also evicted, DNA damage response is attenuated when compared to etoposide. Histone eviction also affects the epigenetic code and deregulates the transcriptome in cancer cells and organs such as the heart. Histone eviction by anthracyclines can drive apoptosis of topoisomerase-negative acute myeloid leukemia blasts in patients. Doxo- and daunorubicin combine the activities of two anti-cancer drugs: etoposide for DNA damage and aclarubicin for histone eviction. We define a novel mechanism of action of anti-cancer drugs doxo- and daunorubicin on chromatin biology with profound consequences on DNA damage responses, epigenetics, transcription, side effects and anti-cancer activities.
|Comparison of histone occupancy of cells or tissues treated with topoisomerase II inhibitors to un-treated ones by FAIRE-seq.
|Qiao X, Pang B, Velds A, Kerkhoven R, van Tellingen O, Neefjes J
|Nov 11, 2011
|Last update date
|May 15, 2019
|3165 Porter Drive
|Illumina Genome Analyzer IIx (Homo sapiens)
|Illumina HiSeq 2000 (Homo sapiens)
|Illumina HiSeq 2000 (Mus musculus)
|This SubSeries is part of SuperSeries:
|Topoisomerase II inhibitors and histone eviction