The isoflavone genistein selectively derepresses major satellite repeat transcription in mouse heterochromatin
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PROVIDER: PRJNA1235182 | ENA |
REPOSITORIES: ENA
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Project description:The isoflavone genistein selectively derepresses major satellite repeat transcription in mouse heterochromatin [Top2beta]
| PRJNA1236257 | ENA
Project description:Heterochromatin has crucial functions in protecting genome integrity. In mouse cells, heterochromatin is characterized by A/T-rich, 234 bp DNA repeat arrays, called the major satellite repeats (MSR). We investigated MSR expression in response to a variety of stress conditions by using small molecule compounds. We identified the isoflavone genistein to selectively derepress MSR transcription but not that of other DNA repeat elements. Genistein is a natural compound that is frequently used in dietary supplements and has been associated with reducing cancer risk. A 24 hrs exposure of mouse embryonic fibroblasts (MEF) to genistein results in a more than 100-fold induction of MSR transcripts. This derepression depends on the activity of RNA polymerase II and requires a cycling G1 cell population. Blocking the cell cycle at the G2/M stage significantly attenuates genistein- mediated derepression of MSR transcription. Mechanistically, DNA topoisomerase poisons phenocopy the genistein-dependent desilencing of MSR expression. Together, these data suggest that MSR transcriptional response is guided by an altered topology of the underlying A/T-rich MSR DNA repeat arrays. In addition, the data reveal a novel function for genistein in derepressing MSR transcription that may contribute to the growth inhibitory and anticancer properties of this natural compound.
2025-09-03 | GSE291747 | GEO
Project description:Heterochromatin has crucial functions in protecting genome integrity. In mouse cells, heterochromatin is characterized by A/T-rich, 234 bp DNA repeat arrays, called the major satellite repeats (MSR). We investigated MSR expression in response to a variety of stress conditions by using small molecule compounds. We identified the isoflavone genistein to selectively derepress MSR transcription but not that of other DNA repeat elements. Genistein is a natural compound that is frequently used in dietary supplements and has been associated with reducing cancer risk. A 24 hrs exposure of mouse embryonic fibroblasts (MEF) to genistein results in a more than 100-fold induction of MSR transcripts. This derepression depends on the activity of RNA polymerase II and requires a cycling G1 cell population. Blocking the cell cycle at the G2/M stage significantly attenuates genistein- mediated derepression of MSR transcription. Mechanistically, DNA topoisomerase poisons phenocopy the genistein-dependent desilencing of MSR expression. Together, these data suggest that MSR transcriptional response is guided by an altered topology of the underlying A/T-rich MSR DNA repeat arrays. In addition, the data reveal a novel function for genistein in derepressing MSR transcription that may contribute to the growth inhibitory and anticancer properties of this natural compound.
2025-09-03 | GSE291959 | GEO
Project description:Establishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on the assessment of the role of this isoflavone in regulation of expression of psoriasis-related genes stands for the present study. The hypothesis tested was that genistein modulates activity of psoriasis-related genes, by reducing the expression efficiency of genes revealing enhanced activity in psoriatic cells, and by stimulating the expression efficiency of genes revealing decreased activity in psoriatic cells. Results provide important information concerning the extent of action of genistein at the molecular level in terms of modulation of gene expression by this substance.
2016-01-01 | GSE60971 | GEO
Project description:Around one sixth of breast cancer cases are classified as triple-negative breast cancer (TNBC), named after the absence of the expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2); however, patients with TNBC suffer from poor clinical outcome and shortage of targeted therapy. Genistein, an estrogenic soy isoflavone, shows anti-cancer effects in TNBC cells such as inducing G2/M cell cycle arrest and apoptosis. However, the underlying mechanism of its anti-cancer effects is poorly understood and its elucidation can help the development of novel therapeutic strategies for TNBC. In this study, by combining isobaric tag-based TMT labeling with titanium dioxide-based phosphopeptide enrichment, we quantitated 5,445 phosphorylation sites on 2,008 phosphoproteins in a TNBC cell line, MDA-MB-231, upon genistein treatment. Our analysis revealed 332 genistein-regulated phosphorylation sites on 226 proteins. Our data show that genistein can regulate several biological processes during the cell cycle, including DNA replication, cohesin complex cleavage, and kinetochore formation. In the meantime, genistein can also activate DNA damage response, including activation of ATR and BRCA1 complex. Overall, for the first time, our study present the evidence that genistein could inhibit TNBC cell growth by regulating the cell cycle and DNA damage response. Our findings help elucidate the mechanisms through which genistein exerts its anti-cancer effects in TNBC cells.
2016-01-26 | PXD002735 | Pride
Project description:Establishment of a transcriptomic profile of human cells treated with genistein with particular emphasis on the assessment of the role of this isoflavone in regulation of expression of psoriasis-related genes stands for the present study. The hypothesis tested was that genistein modulates activity of psoriasis-related genes, by reducing the expression efficiency of genes revealing enhanced activity in psoriatic cells, and by stimulating the expression efficiency of genes revealing decreased activity in psoriatic cells. Results provide important information concerning the extent of action of genistein at the molecular level in terms of modulation of gene expression by this substance. Total RNA obtained from human immortalized keratinocyte (HaCaT) subjected to 24 or 48 hours in vitro exposure to 30, 60 or 100 µM genistein, or 0.05%DMSO (K).
2016-07-03 | E-GEOD-60971 | biostudies-arrayexpress
Project description:Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP) and interleukin-6 (IL-6) via effects on Smad4 or Stat3, respectively. We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression. We found that treatment with the isoflavone genistein from 28−52 hours post-fertilization in zebrafish embryos enhanced Hepcidin transcript levels as assessed by whole mount in situ hybridization and quantitative realtime RT-PCR. Genistein’s stimulatory effect was conserved in human hepatocytes: genistein treatment of HepG2 cells increased both Hepcidin transcript levels and Hepcidin promoter activity. We found that genistein’s effect on Hepcidin expression did not depend on estrogen receptor signaling or increased cellular iron uptake, but was impaired by mutation of either the BMP response elements or the Stat3 binding site in the Hepcidin promoter. RNA-sequencing of transcripts from genistein-treated hepatocytes indicated that genistein upregulated 68% of the transcripts that were upregulated by BMP6, however genistein raised the levels of several transcripts involved in Stat3 signaling that were not upregulated by BMP6. Chromatin-immunoprecipitation and ELISA experiments revealed that genistein enhanced Stat3 binding to the Hepcidin promoter and increased phosphorylation of Stat3 in HepG2 cells. CONCLUSION: Genistein is the first small molecule experimental drug that stimulates Hepcidin expression in vivo and in vitro. These experiments demonstrate the feasibility of identifying and characterizing small molecules that increase Hepcidin expression. Genistein and other candidate molecules may subsequently be developed into new therapies for iron overload syndromes.
2015-08-13 | GSE40069 | GEO
Project description:Repeatome profiling across ovarian, pancreatic, and colorectal cell lines identifies distinct clustering that is independent of tissue of origin highlighting differences in repeat co-expression patterns. Deeper analysis of ovarian cancer cell lines demonstrated that HSATII satellite repeat expression was highly associated with epithelial mesenchymal transition (EMT) and anti-correlated with interferon (IFN) response genes indicative of a more aggressive phenotype.
2022-06-06 | GSE205430 | GEO
Project description:m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin
2021-04-21 | GSE156481 | GEO
Project description:Granulocyte colony-stimulating factor (G-CSF) has been utilized to treat neutropenia in various clinical settings. Although clearly beneficial, there are concerns that use of G-CSF in certain conditions increases the risk of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The most striking example is in severe congenital neutropenia (SCN). SCN patients develop MDS/AML at a high rate that is directly correlated to the cumulative lifetime dosage of G-CSF. MDS and AML that arise in these settings are commonly associated with chromosomal deletions. We demonstrate that chronic G-CSF treatment in mice results in expansion of the hematopoietic stem cell population. Furthermore, primitive hematopoietic progenitors from G-CSF–treated mice show evidence of DNA damage as demonstrated by an increase in double strand breaks and recurrent chromosomal deletions. Concurrent treatment with genistein, a natural soy isoflavone, limits DNA damage in this population. The protective effect of genistein appears to be related to its preferential inhibition of G-CSF–induced proliferation of hematopoietic stem cells. Importantly, genistein does not impair G-CSF–induced proliferation of committed hematopoietic progenitors, nor diminish neutrophil production. The protective effect of genistein was accomplished with plasma levels that are easily attainable through dietary supplementation. aCGH was performed using NimbleGen
2014-02-07 | GSE54737 | GEO