Project description:In vitro maturation (IVM) oocyte is a key component of assisted reproduction in pigs. Asynchronous nucleoplasmic maturation and incomplete cytoplasmic maturation is one of the key factors for impaired maturation and quality of oocytes matured in vitro. Although Single-omics techniques have been applied to the study of porcine oocyte maturation mechanisms in the past, it is difficult to address a systematic and comprehensive explanation of the complex maturation regulatory network through Single-omics data alone, and it is insufficient to account for the chain of transmission of the regulation of genetic information expression. This is the first study which determine the gene transcripts, host potential proteins interactions, and key functional metabolites involved in the maturation mechanism of porcine oocytes. We found that among 2624 and 124 differentially expressed genes and proteins respectively, genes DNMT1, HENMT1, H1FOO, GDF9, NUP214, CAST and GSTM3 were differentially coexisted at both levels,these differentially expressed genes are closely associated with 13 differentially expressed metabolites.In addition, the genes DNMT1 , HENMT1, H1FOO, GDF9, NUP214, CAST and GSTM3 were differentially expressed at both transcript and protein levels. To address further functional analysis, we conducted GO and KEGG analysis at mRNAs and metabolites level to outcome the involvement of multiple epigenetic regulatory mechanisms affecting nuclear and cytoplasmic maturation of porcine oocytes. Thus, we systematically illustrated how epigenetic modifications affect nuclear and cytoplasmic maturation of porcine oocytes from the dimension of the transmission chain of genetic information expression regulation. Specifically, it includes: 1) .The increase in DNA methylation level and the decrease in histone acetylation level lead to the reduction of chromatin accessibility, thereby triggering global transcriptional silencing. 2).A large number of mRNAs that have been transcribed in the nucleus need to undergo complex modifications before they can be recognized by the nuclear pore complex (NPC) and transported to the cytoplasm. 3). The mRNAs transported to the cytoplasm are selectively translated activated according to the requirements of the cell maturation process. This spatiotemporal heterogeneity of translation activation is strictly regulated by post-transcriptional modifications. 4 ). Post-translational modifications regulate the active sialic acid metabolism to prepare for the fertilization process; the macro and micro changes in glutathione metabolism and mitochondrial metabolism aim to meet the dynamic energy requirements of the cell and regulate intracellular redox homeostasis to reduce oxidative damage.
Project description:<p>Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood. In this study, we observe the higher levels of histone serotonylation (H3K4me3Q5ser) and transglutaminases 2 (TGM2, the enzyme catalyzing serotonylation) in both pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in comparison with their normal counterparts, and inhibition of histone serotonylation suppresses PDAC development. Mechanistically, we demonstrate that TGM2-mediated histone serotonylation at promoter of the gene encoding stearoyl-CoA desaturase (SCD) up-regulates its expression and drives PDAC development by lipid metabolism remodeling. Collectively, this study reveals histone serotonylation as an important driver of PDAC tumorigenesis.Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood. In this study, we observe the higher levels of histone serotonylation (H3K4me3Q5ser) and transglutaminases 2 (TGM2, the enzyme catalyzing serotonylation) in both pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in comparison with their normal counterparts, and inhibition of histone serotonylation suppresses PDAC development. Mechanistically, we demonstrate that TGM2-mediated histone serotonylation at promoter of the gene encoding stearoyl-CoA desaturase (SCD) up-regulates its expression and drives PDAC development by lipid metabolism remodeling. Collectively, this study reveals histone serotonylation as an important driver of PDAC tumorigenesis.</p>
Project description:Aberrations in histone post-translational modifications (PTMs), as well as in the histone modifying enzymes (HMEs) that catalyze their deposition and removal, have been reported in many tumors, and many epigenetic inhibitors are currently under investigation for cancer treatment. Therefore, profiling epigenetic features in cancer could have important implications for the discovery of both biomarkers for patient stratification and novel epigenetic targets. In this study, we employed mass spectrometry based approaches to comprehensively profile histone H3 PTMs in a panel of normal and tumoral tissues for different cancer models
Project description:Epigenetic modifications directly regulate the patterns of gene expression by altering DNA accessibility and chromatin structure. A knowledge gap is presented by the need to directly measure these modifications, especially for unannotated organisms with unknown primary histone sequences. In the present work, we developed and applied a novel workflow for identifying and annotating histone proteoforms directly from mass spectrometry-based measurements for the endangered Caribbean coral Acropora cervicornis. Combining high accuracy de novo top-down and bottom-up analysis based on tandem liquid chromatography, trapped ion mobility spectrometry, non-ergodic electron-based fragmentation, and high-resolution mass spectrometry, near complete primary sequence (up to 99%) and over 86 post-translational modification annotations were obtained from pull-down histone fractions. In the absence of reliable genome annotations, H2A, H2B and H4 histone sequences and the annotation of the post-translational modifications of the stressed A. cervicornis coral allow for a better understanding of chromatin remodeling and new strategies for target intervention and restoration of endangered reef corals.
Project description:Both genetic and environmental factors are implicated in Type 1 Diabetes (T1D). Since environmental factors can trigger epigenetic changes, we hypothesized that variations in histone posttranslational modifications (PTMs) at the promoter/enhancer regions of T1D susceptible genes may be associated with T1D. We therefore evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the chromatin-immunoprecipitation-linked-to-microarray approach to profile key histone PTMs, including H3-lysine-4 trimethylation (H3K4me3), H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac at genes within the T1D susceptible loci in lymphocytes, and H3K4me3, H3K9me2, H3K9Ac and H4K16Ac at the IDDM1 region in monocytes of T1D patients and healthy controls separately. We screened for potential variations in histone PTMs using computational methods to compare datasets from T1D and controls. Interestingly, we observed marked variations in H3K9Ac levels at the upstream regions of HLA-DRB1 and HLA-DQB1 within the IDDM1 locus in T1D monocytes relative to controls. Additional experiments with THP-1 monocytes demonstrated increased expression of HLA-DRB1 and HLA-DQB1 in response to interferon- and TNF-treatment that were accompanied by changes in H3K9Ac at the same promoter regions as that seen in the patient monocytes. These results suggest that the H3K9Ac status of HLA-DRB1 and HLA-DQB1, two genes highly associated with T1D, may be relevant to their regulation and transcriptional response towards external stimuli. Thus, the promoter/enhancer architecture and chromatin status of key susceptible loci could be important determinants in their functional association to T1D susceptibility. We evaluated histone PTM variations at known T1D susceptible genes in blood cells from T1D patients versus healthy non-diabetic controls, and explored their connections to T1D. We used the ChIP-chip approach to profile key histone PTMs, including histone H3K4me3, H3K27me3, H3K9me3, H3K9 acetylation (H3K9Ac) and H4K16Ac, at genes within the T1D susceptible loci in lymphocytes.
Project description:We characterize the epigenome of the human malaria vector Anopheles gambiae in midgut cells by mapping the distribution and levels of two post-translational histone modifications, H3K27ac and H3K27me3. These histone profiles were then correlated with levels of gene expression obtained by RNA-seq.