Epigenetic selectivity of TopoIIα redistribution and histone eviction of anthracyclines
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ABSTRACT:
PROVIDER: PRJNA1003812 | ENA |
REPOSITORIES: ENA
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Project description:Anthracyclines act by disrupting the interface of TopoII and DNA and by evicting histones. The anthracycline-specific redistribution of TopoII and its association with histone eviction were addressed in K562 cells. Chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) against endogenously tagged TopoIIα, and transposase-accessible chromatin with sequencing (ATAC-seq) was performed 4 hours after anthracycline exposure.
2023-08-11 | GSE240443 | GEO
Project description: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.
2013-06-04 | E-GEOD-33632 | biostudies-arrayexpress
Project description: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.
2013-06-04 | GSE33632 | GEO
Project description:Topoisomerase II inhibitors and histone eviction
| PRJNA148617 | ENA
Project description:One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. Here, we compare three members of this class - the antracyclines doxorubicin and aclarubicin, and a chemically unrelated compound, etoposide. Aclarubicin does not induce DNA breaks. We define a new activity for the antracyclines: unsupported histone eviction from ´open´ or loosely packed chromosomal areas reflecting exon and promoter regions. Comparison of histone H3K4me3 of cells post topoisomerase II inhibitors treatment to un-treated ones by ChIP-seq. Comparison of phosphorylated histone H2AX of cells post topoisomerase II inhibitors doxorubicin and etoposide treatment to un-treated ones by ChIP-seq.
2013-06-04 | E-GEOD-33633 | biostudies-arrayexpress
Project description:One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. Here, we compare three members of this class - the antracyclines doxorubicin and aclarubicin, and a chemically unrelated compound, etoposide. Aclarubicin does not induce DNA breaks. We define a new activity for the antracyclines: unsupported histone eviction from ´open´ or loosely packed chromosomal areas reflecting exon and promoter regions.
2013-06-04 | GSE33633 | GEO
Project description:Genome-wide analysis of histone eviction by FAIRE-Seq
| PRJNA154327 | ENA
Project description:We propose that H3K4ac acts as marker of active TSSs and enhancers and plays roles in histone eviction and RNA transcription.
2024-11-12 | GSE248434 | GEO
Project description:Plants can sense temperature changes and adjust their development and morphology accordingly in a process called thermomorphogenesis. This phenotypic plasticity implies complex mechanisms regulating gene expression reprogramming in response to environmental alteration. Histone variants contribute to the chromatin dynamics and transcriptional control, yet how their deposition/eviction modulates transcriptional changes induced by environmental cues remains elusive. In Arabidopsis thaliana, temperature elevation-induced transcriptional activation at thermo-responsive genes entails the chromatin eviction of a histone variant H2A.Z by INO80, which is recruited to these loci via interacting with a key thermomorphogenesis regulator PHYTOCHROME-INTERACTING FACTOR 4 (PIF4). Here, we show that both INO80 and the deposition chaperones of another histone variant H3.3 associate with EARLY FLOWERING7 (ELF7), a critical component of the transcription elongation factor polymerase-associated factor 1 complex (PAF1c). H3.3 promotes thermomorphogenesis and the high temperature-enhanced RNA Pol II transcription at PIF4 targets, and it is broadly required for the H2A.Z removal-induced gene activation. Reciprocally, INO80 and ELF7 regulate H3.3 deposition, and are necessary for the high temperature-induced H3.3 enrichment at PIF4 targets. Our findings demonstrate close coordination between H2A.Z eviction and H3.3 deposition in gene activation induced by high temperature, and pinpoint the importance of histone variants dynamics in transcriptional regulation.
2023-01-13 | GSE221657 | GEO
Project description:Plants can sense temperature changes and adjust their development and morphology accordingly in a process called thermomorphogenesis. This phenotypic plasticity implies complex mechanisms regulating gene expression reprogramming in response to environmental alteration. Histone variants contribute to the chromatin dynamics and transcriptional control, yet how their deposition/eviction modulates transcriptional changes induced by environmental cues remains elusive. In Arabidopsis thaliana, temperature elevation-induced transcriptional activation at thermo-responsive genes entails the chromatin eviction of a histone variant H2A.Z by INO80, which is recruited to these loci via interacting with a key thermomorphogenesis regulator PHYTOCHROME-INTERACTING FACTOR 4 (PIF4). Here, we show that both INO80 and the deposition chaperones of another histone variant H3.3 associate with EARLY FLOWERING7 (ELF7), a critical component of the transcription elongation factor polymerase-associated factor 1 complex (PAF1c). H3.3 promotes thermomorphogenesis and the high temperature-enhanced RNA Pol II transcription at PIF4 targets, and it is broadly required for the H2A.Z removal-induced gene activation. Reciprocally, INO80 and ELF7 regulate H3.3 deposition, and are necessary for the high temperature-induced H3.3 enrichment at PIF4 targets. Our findings demonstrate close coordination between H2A.Z eviction and H3.3 deposition in gene activation induced by high temperature, and pinpoint the importance of histone variants dynamics in transcriptional regulation.
2023-01-13 | GSE207365 | GEO