Project description:Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5 kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.
Project description:Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5 kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.
Project description:MYC is a driver oncogene in many cancers. Inhibition of MYC promises high therapeutic potential, but specific MYC inhibitors remain unavailable for clinical use. Previous studies suggest that MYC amplified Medulloblastoma cells are vulnerable to HDAC inhibition. Using co-immunoprecipitation, mass spectrometry and ChIP-sequencing we show that HDAC2 is a cofactor of MYC in MYC amplified primary medulloblastoma and cell lines. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein inducing a down-regulation of MYC activated genes (MAGs) and up-regulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and distinct E-box distribution. We conclude that MYC and HDAC2 (class I) are localized in a complex in MYC amplified medulloblastoma and drive a MYC-specific transcriptional program, which is reversed by the class I HDAC inhibitor entinostat. Thus, the development of HDAC inhibitors for treatment of MYC amplified medulloblastoma should include HDAC2 in its profile in order to directly target MYC´s trans-activating and trans-repressing function.
2020-09-01 | GSE143376 | GEO
Project description:High-throughput sequencing of environments
| PRJNA561896 | ENA
Project description:Metagenome assembled genomes (MAGs) from cellulose enrichments of the Black Sea sulfidic waters. Metagenomic assembly