Project description:The aim was to characterize epigenetic changes in histone proteins during callus formation from roots and shoots of Arabidopsis thaliana seedlings using mass spectrometry-based approach. Increased level of histone H3.3 variant was found to be the most prominent feature of 20-day-old calli, associated with chromatin relaxation. Methylation status in root- and shoot-derived calli reached the same level during long-term propagation, whereas differences in acetylation levels provided a long-lasting imprint of root and shoot origin. On the other hand, epigenetic signs of origin completely disappeared during 20 days of calli propagation in the presence of histone deacetylase inhibitors (HDACi), sodium butyrate and trichostatin A, although each HDACi affected the state of post-translational histone modifications in a specific manner.
Project description:Commensal bacteria shape the gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms are not yet known. To reveal the mechanism, we isolated naïve CD4+ T cells from the spleen of C57BL/6 mice and cultured the cells under Treg-inducing condition culture in the presence or absence of butyrate, a metabolite produced by commensal bacteria. Naïve T cells were isolated from spleen and were cultured in the presence of IL-2, TGF-beta and in the presence or absene of Butyrate. RNA was extracted at Day 2.
Project description:This SuperSeries is composed of the following subset Series: GSE15107: R1 mESC Exposed to Butyrate GSE15109: BG02 hESC Exposed to Butyrate GSE15110: H1 hESC Exposed to Butyrate Refer to individual Series
Project description:Epigenetic modifying enzymes are commonly mutated in diffuse large B cell lymphoma (DLBCL), suggesting that epigenetic regulation is an important factor in DLBCL pathogenesis and a potential target for therapy. We developed resistant cell lines to histone deacetylase inhibitors (HDACi), one such epigenetic therapy, in order to define mechanisms of response and resistance. Strikingly, using gene expression and metabolic profiling, we found that development of HDACi resistance was associated with differentiation toward a plasmablast-like phenotype. Differentiation correlated with decreased B cell receptor signaling, increased ER stress and activation of the unfolded protein response, and increased sensitivity to proteasome inhibitors. Importantly, we found evidence of differentiation in lymphoma biopsies from patients treated with HDACi. Together, these data show, for the first time, that HDACi are differentiating agents in lymphoma and may be used to prime DLBCL for targeted therapy including proteasome inhibitors. Gene expression in DLBCL cells from tumor biopsies after 15 days panobinostat therapy
Project description:Commensal bacteria shapes gut immune system. Colonization bacteria increase the frequency of regulatory T cells, however, the molecular mechanisms has not yet been unknown. To reveal the mechanism, we isolated NaM-CM-/ve CD4+ T cells from spleen of C57BL/6 mice and cultured the cells under Treg-inducing condition culture in the presence or absence of butyrate, a metabolite produced by commensal bacteria. NaM-CM-/ve T cells were isolated from spleen and were cultured in the presence of IL-2, TGF-beta and in the presence or absene of Butyrate. RNA was extracted at Day 2
Project description:Here, we examined the therapeutic utility of EC359 in improving the therapeutic efficacy of HDACi in TNBC models. BT-549 cells were treated with vehicle (DMSO), EC359, HDACi(Vorinostat), EC359+HDACi and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that the beneficial effect of the EC359+HDACi involves regulation of multiple genes that involved in several pathways including apoptosis, metabolism and cell cycle.
Project description:We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process. We identified several thousand specific regulatory elements (~10% of total DHS sites) that become significantly more or less accessible with sodium butyrate or suberanilohydroxamic acid (SAHA) 72-hour treatments. Most of the differential DNase-hypersensitive (DHS) sites display hallmarks of enhancers; including being enriched for non-promoter regions, associated with nearby gene expression changes, and capable of increasing luciferase reporter expression in K562 cells. Differential DHS sites were enriched for key hematopoietic lineage transcription factor motifs, including SPI1 (PU.1), a known pioneer factor. We found PU.1 becomes up-regulated and increases binding at opened DHS sites by ChIP-seq with HDACi treatment, but show that increased PU.1 protein levels alone are sufficient for only modest increases in chromatin accessibility. PU.1 knockdown by shRNA failed to block the HDACi-induced chromatin accessibility and expression changes in K562, suggesting factors other than PU.1 are responsible for establishment of active enhancers in the HDACi induced differentiation process.
Project description:To assess the effect of sodium butyrate exposure on human ESC grown without culture support for self-renewal (I.e. without conditioned medium and added bFGF) - three groups were compared - H1 culture in feeder conditioned medium vs without conditioned medium in 0.2 mM sodium butyrate vs. grown in sodium butyrate for 4 passages followed by return to conditioned medium conditions for 3 passages. The three groups were grown in triplicate and compared on Agilent whole human genome array