Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1297984 | ENA |
REPOSITORIES: ENA
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Project description:The integrated activity of cis-regulatory elements fine-tunes transcriptional programs of mammalian cells by recruiting cell type–specific as well as ubiquitous transcription factors (TFs). Despite their key role in modulating transcription, enhancers are still poorly characterized at the molecular level, and their limited DNA sequence conservation in evolution and variable distance from target genes make their unbiased identification challenging. The coexistence of high mono-methylation and low tri-methylation levels of lysine 4 of histone H3 is considered a signature of enhancers, but a comprehensive view of histone modifications associated to enhancers is still lacking. By combining chromatin immunoprecipitation (ChIP) with mass spectrometry, we investigated cis-regulatory regions in macrophages to comprehensively identify histone marks specifically associated with enhancers, and to profile their dynamics after transcriptional activation elicited by an inflammatory stimulation. The intersection of the proteomics data with ChIP-seq and RNA-seq analyses revealed the existence of novel subpopulations of enhancers, marked by specific histone modification signatures: specifically, H3K36me2/K4me1 marks transcribed enhancers, while H3K36me3/K4me1 and H3K79me2/K4me1 combinations mark distinct classes of intronic enhancers. Thus, our MS analysis of functionally distinct genomic regions revealed the combinatorial code of histone modifications, highlighting the potential of proteomics in addressing fundamental questions in epigenetics.
2017-10-09 | PXD007582 | Pride
Project description:Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. We here demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed a broad pattern of histone lactylation at various genes in CD4+ T cells, with particularly highly enriched lactylation of histone H3 at the Foxp3 promoter regions in lactate-treated Th17 cells. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotype into regulatory T cells. Moreover, we show that high lactate concentrations suppress the Th17 pathogenicity during intestinal inflammation. Collectively, these findings have a potential therapeutic value for development of novel clinical strategies to target inflammatory and autoimmune diseases.
2022-11-25 | GSE208727 | GEO
Project description:Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in diminished H3K9ac
expression, loss of stem cells, and robust activation of interferon signaling. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and dsRIP-seq were employed to interrogate the mechanism behind this response, which identified self-derived, mitochondria- encoded double-stranded RNA as the source of intrinsic interferon signaling. KAT2A and KAT2B therefore play an essential role in regulating mitochondrial functions as well as maintaining intestinal health.
2023-07-07 | MSV000092370 | MassIVE
Project description:Dexmedetomidine (DEX) was served to controlling the over-reactive inflammatory effects to protect from the sepsis-induced organ failure via modulating histone methylation. However, the genome-wide changes of histone methylations upon DEX for sepsis treatment were poorly explored. (AKI) mouse model was induced by lipopolysaccharide (LPS), and added DEX (AKI+D) and KDM5A-IN-1 (KDM5A inhibitor) (AKI+K) respectively. ChIP-seq to investigate the H3K4me3 pattern in renal cortex tissues. Each group has two replications.
2020-07-03 | E-MTAB-8133 | biostudies-arrayexpress
Project description:SALL4 ensures oocytes maturation by modulating DNA methylation and histone modifications (RNA-Seq)
| PRJNA335647 | ENA
Project description:STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4+ T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4+ T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis. This SuperSeries is composed of the following subset Series: GSE21669: Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis [ChIP-seq] GSE21670: Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis [Affymetrix Expression] Refer to individual Series
2010-05-29 | E-GEOD-21671 | biostudies-arrayexpress
Project description:The development and severity of inflammatory bowel diseases (IBD) and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that intestinal epithelial cells (IECs) isolated from IBD patients exhibit decreased expression of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3). Further, genome-wide analyses of murine IECs that lack HDAC3 (HDAC3ΔIEC) revealed that HDAC3 deficiency resulted in dysregulated gene expression coupled with alterations in histone acetylation. Critically, conventionally-housed HDAC3ΔIEC mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3ΔIEC mice exhibited significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 plays a central role in maintaining intestinal homeostasis. Strikingly, rederivation of HDAC3ΔIEC mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis, and intestinal barrier function were largely restored in the absence of commensal bacteria. Collectively, these data indicate that the HDAC3 is a critical factor that integrates commensal bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis. Analyses of histone acetylation in primary IECs from HDAC3FF (3 biologic replicates) and HDAC3ΔIEC (3 biologic replicates) mice were conducted utilizing ChIP-seq for H3K9Ac.
2013-12-02 | E-GEOD-50453 | biostudies-arrayexpress
Project description:Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing [RNA-seq, transdifferentiation]
| PRJNA1128675 | ENA
Project description:Interventions: Music group:Listening the music;ambient sound group:none;no sound group:Earplugs cut off sound
Primary outcome(s): pan-immune-inflammation value,PIV;defined daily dose, DDD
Study Design: Parallel
| 105523 | ecrin-mdr-crc