Transcriptional memory is conferred by combined heritable maintenance and local removal of selective chromatin modifications
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1047536 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Interferon-γ (IFNγ) transiently activates genes involved in inflammation and innate immunity. A subset of targets maintain a mitotically heritable memory of prior IFNγ exposure resulting in hyperactivation upon reexposure. Here we discovered that the active chromatin marks H3K4me1, H3K14Ac and H4K16Ac are established during IFNγ priming and selectively maintained on a cluster of GBP genes for at least 7 days in dividing cells in the absence of transcription. The histone acetyltransferase KAT7 is required for the accelerated GBP reactivation upon reexposure to IFNγ. In naïve cells, we find the GBP cluster is maintained in low-level repressive chromatin marked by H3K27me3 limiting priming in a PRC2-dependent manner. Unexpectedly, IFNγ results in transient accumulation of this repressive mark but is then selectively depleted from primed GBP genes during the memory phase facilitating hyperactivation of primed cells. Furthermore, we identified a cis-regulatory element that makes transient, long-range contacts across the GBP cluster and acts as a repressor, primarily to curb the hyperactivation of previously IFNγ-primed cells. Combined our results identify the putative chromatin basis for long-term transcriptional memory of interferon signalling that may contribute to enhanced innate immunity.
2025-01-20 | GSE249136 | GEO
Project description:Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. Here we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy.
2021-02-22 | GSE161654 | GEO
Project description:There is growing evidence that paternal pre-conception cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring. To characterize the effects of CS exposure on the sperm epigenome and offspring neurodevelopment, we investigated the impact of pre-conception paternal CS exposure on mouse sperm DNA methylation and gene expression in offspring. We further investigated the role of oxidative stress on sperm epigenetic changes using a mouse model (Nrf-/-) with impaired antioxidant capacity. Lastly, we evaluated the capacity for sperm DNA methylation to recover following removal of CS for 1-5 spermatogenic cycles (28-171 days). We found that smoking significantly impacts sperm DNA methylation as well as DNA methylation and gene expression in offspring. These changes were largely recapitulated in Nrf-/- mice independent of smoke exposure. Recovery experiments indicated that about half of differentially methylated regions returned to normal within 28 days of removal from smoke, however additional recovery following longer periods was not observed. Thus, we present strong evidence that cigarette smoke exposure induces paternally mediated, heritable epigenetic changes. Parallel studies performed in Nrf-/- mice provide evidence for oxidative stress as the predominant underlying mechanism for smoke-induced epigenetic changes to sperm as well as changes in the offspring of smoke-exposed sires. Lastly, recovery experiments indicate that while many epigenetic changes are corrected following removal from smoke exposure, aberrant methylation persists at a significant number of regions even after five spermatogenic cycles
2020-05-06 | GSE133739 | GEO
Project description:Human twin studies have revealed the combined contribution of heritable and non-heritable (environmental) factors in shaping peripheral blood immune system variability. However, the heterogeneity within tissue immune compartments and the contribution of tissue-specific external factors remain unexplored. The human uterus is a tissue under constant regeneration exposed to distinct environmental factors. To assess uterine immune system variation, we have performed a transcriptomic and epigenetic analysis of uterine and peripheral blood immune cells in monozygotic twins and longitudinal samples in relation to heritable versus non-heritable factors.
2024-04-12 | GSE225040 | GEO
Project description:Human twin studies have revealed the combined contribution of heritable and non-heritable (environmental) factors in shaping peripheral blood immune system variability. However, the heterogeneity within tissue immune compartments and the contribution of tissue-specific external factors remain unexplored. The human uterus is a tissue under constant regeneration exposed to distinct environmental factors. To assess uterine immune system variation, we have performed a transcriptomic and epigenetic analysis of uterine and peripheral blood immune cells in monozygotic twins and longitudinal samples in relation to heritable versus non-heritable factors.
2024-04-12 | GSE225041 | GEO
Project description:There is growing evidence that paternal pre-conception cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring. To characterize the effects of CS exposure on the sperm epigenome and offspring neurodevelopment, we investigated the impact of pre-conception paternal CS exposure on mouse sperm DNA methylation and gene expression in offspring. We further investigated the role of oxidative stress on sperm epigenetic changes using a mouse model (Nrf-/-) with impaired antioxidant capacity. Lastly, we evaluated the capacity for sperm DNA methylation to recover following removal of CS for 1-5 spermatogenic cycles (28-171 days). We found that smoking significantly impacts sperm DNA methylation as well as DNA methylation and gene expression in offspring. These changes were largely recapitulated in Nrf-/- mice independent of smoke exposure. Recovery experiments indicated that about half of differentially methylated regions returned to normal within 28 days of removal from smoke, however additional recovery following longer periods was not observed. Thus, we present strong evidence that cigarette smoke exposure induces paternally mediated, heritable epigenetic changes. Parallel studies performed in Nrf-/- mice provide evidence for oxidative stress as the predominant underlying mechanism for smoke-induced epigenetic changes to sperm as well as changes in the offspring of smoke-exposed sires. Lastly, recovery experiments indicate that while many epigenetic changes are corrected following removal from smoke exposure, aberrant methylation persists at a significant number of regions even after five spermatogenic cycles
2020-05-06 | GSE133740 | GEO
Project description:nitrogen removal bioreactors Raw sequence reads
| PRJNA559751 | ENA
Project description:Ammonium removal through Bioelectrochemical systems
| PRJEB75202 | ENA
Project description:Local calcium accumulations promote phagocyte-mediated synapse removal in cortical neuroinflammation
| PRJNA679032 | ENA