A unidirectional histone code in bidirectional promoters across cell types
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PROVIDER: EGAS00001001656 | EGA |
REPOSITORIES: EGA
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Project description:Nucleosomes are the building blocks of chromatin where gene regulation takes place. Chromatin landscapes have been profiled for several species, providing insights into the understanding of fundamental mechanisms of chromatin-mediated transcriptional regulation of gene expression. However, knowledge is missing from several major and deep-branching eukaryotic groups, such as the marine model diatom Phaeodactylum tricornutum. Diatoms are highly diverse and ubiquitous species of phytoplankton that play a key role in global biogeochemical cycles. Dissecting chromatin-mediated regulation of genes in diatoms will help understand the ecological success of these organisms in contemporary oceans. Here, we use high resolution mass spectrometry to identify a full repertoire of post-translational modifications on P. tricornutum histones, including eight novel modifications. We map five histone marks coupled with expression data and show that P. tricornutum displays both unique and broadly conserved chromatin features, reflecting the chimeric nature of its genome. Combinatorial analysis of histone marks and DNA methylation demonstrates the presence of an epigenetic code defining active or repressive chromatin states. We further profile three specific histone marks under conditions of nitrate depletion and show that the histone code is dynamic and targets specific sets of genes. This study is the first genome-wide characterization of the histone code from a Stramenopile and a marine phytoplankton. The work represents an important initial step for understanding the evolutionary history of chromatin and how epigenetic modifications affect gene expression in response to environmental cues in marine environments.
2015-05-08 | PXD002148 | Pride
Project description:Chemical modifications to the tails of histone proteins act as gene regulators that play a pivotal role in adaptive responses to environmental stress. Determining the short and long term kinetics of histone marks is essential for understanding their functions in adaptation. We used Caenorhabditis elegans as a model organism to study the histone modification kinetics in response to environmental stress, taking advantage of their ability to live in both terrestrial and aquatic environments. We investigated the multigenerational genome-wide dynamics of five histone marks (H3K4me3, H3K27me3, H4K20me1, H3K36me1, and H3K9me3) by maintaining P0 animals on terrestrial (agar plates), F1 in aquatic cultures, and F2 back on terrestrial environments. We determined the distributions of histone marks in the gene promoter regions and found that H4K20me1, H3K36me1, and H3K9me3 showed up to eleven-fold differences in density, whereas H3K4me3 and H3K27me3 remained highly constant during adaptation from terrestrial to aquatic environments. Furthermore, we predicted that up to five combinations of histone marks can co-occupy single gene promoters and confirmed the colocalization of these histone marks by structured illumination microscopy. The co-occupancy increases with environment changes and different co-occupancy patterns contribute to variances in gene expressions and thereby presents a supporting evidence for the histone code hypothesis.
2021-07-09 | GSE103775 | GEO
Project description:Genome-wide mapping of transcriptional regulatory elements are essential tools for the understanding of the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of nascent, Pol-II-transcribed RNAs by Cap Analysis of Gene Expression (CAGE-Seq) with genome-wide profiling of histones modifications by chromatin immunoprecipitation (ChIP-seq) to map active promoters and enhancers in a model of human neural commitment, represented by embryonic stem cells (ESCs) induced to differentiate into self-renewing neuroepithelial-like stem cells (NESC). We integrated CAGE-seq, ChIP-seq and gene expression profiles to discover shared or cell-specific regulatory elements, transcription start sites and transcripts associated to the transition from pluripotent to neural-restricted stem cell. Our analysis showed that >90% of the promoters are in common between the two cell types, while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a “bivalent” histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provide a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and gene expression programs occurring in the transition from a pluripotent to a neural-restricted cell fate. ESCs (H9 NIH code WA09, ISL1 Ds-Red) were kindly provided by the group of K.R. Chien. Neural differentiation was induced by the method of embryoid bodies following a published protocol [1]. Briefly, 4-days embryoid bodies were transferred to polyornithine-coated dishes and propagated in N2-supplemented DMEM/F12 (Invitrogen). Total RNA was extracted from 1-2x10^6 cells from three different cultures of ESCs and NESCs, transcribed into biotinylatedcRNA and hybridized onto GeneChip® HG-U133 Plus 2.0 Arrays (Affymetrix) according to the protocol supplied by the manufacturer (Affymetrix, Santa Clara, CA).
2015-05-21 | E-GEOD-61266 | biostudies-arrayexpress
Project description:Epigenetic modifications and nucleosome positioning play an important role in modulating gene expression. However, how the patterns of epigenetic modifications and nucleosome positioning are established around promoters is not well understood. Here, we have addressed these questions in a series of genome-wide experiments coupled to a novel bioinformatic analysis approach. Our data reveal a clear correlation between CpG density, promoter activity and accumulation of active or repressive histone marks. CGI boundaries define the chromatin promoter regions that will be epigenetically modified. CpG-rich promoters are targeted by histone modifications and histone variants, while CpG-poor promoters are regulated by DNA methylation. CGIs boundaries, but not transcriptional activity, are essential determinants of H2A.Z positioning in vicinity of the promoters, suggesting that the presence of H2A.Z is not related to transcriptional control. Accordingly, H2A.Z depletion has no impact on gene expression of arrested mouse embryonic fibroblasts. Therefore, the underlying DNA sequence, the promoter CpG density and, to a lesser extent, transcriptional activity, are key factors implicated in promoter chromatin architecture.
2020-10-02 | GSE107303 | GEO
Project description:Genome-wide mapping of transcriptional regulatory elements are essential tools for the understanding of the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of nascent, Pol-II-transcribed RNAs by Cap Analysis of Gene Expression (CAGE-Seq) with genome-wide profiling of histones modifications by chromatin immunoprecipitation (ChIP-seq) to map active promoters and enhancers in a model of human neural commitment, represented by embryonic stem cells (ESCs) induced to differentiate into self-renewing neuroepithelial-like stem cells (NESC). We integrated CAGE-seq, ChIP-seq and gene expression profiles to discover shared or cell-specific regulatory elements, transcription start sites and transcripts associated to the transition from pluripotent to neural-restricted stem cell. Our analysis showed that >90% of the promoters are in common between the two cell types, while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a “bivalent” histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provide a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and gene expression programs occurring in the transition from a pluripotent to a neural-restricted cell fate. Investiagtion of promoters usage changes during ESCs neural induction ESCs and NESCs promoter usage profiling by CAGE-seq
2015-05-21 | E-GEOD-61264 | biostudies-arrayexpress
Project description:Very little is known on the nature of epigenetic states in developing zebrafish despite its growing importance as a model organism in developmental biology. We report histone modifications on promoters of pluripotency genes in zebrafish embryos at the mid-late blastula transition (MBT+) stage. We identify three classes of expressed genes based on these profiles: (1) those with a promoter occupied by marks of active genes without any repressive marks; (2) those co-occupied by both activating and repressive modifications; of these genes, klf4 was notably found to be mosaically expressed in the embryo, possibly accounting for this epigenetic pattern; (3) those occupied by repressive marks with, surprisingly, little not acetylated H3K9 or H4. Culture of embryo-derived cells results in a switch from histone acetylation to K9 and K27 trimethylation on genes transcriptionally inactivated, resulting in a profile similar to that of fibroblasts. All promoters retain H3K4me3, indicating no correlation between H3K4me3 occupancy and gene expression. Our results illustrate a complex chromatin state on the promoter of pluripotency-associated genes in the zebrafish embryo, shortly after the embryonic genome is turned on. We assessed gene expression in unfertilized eggs and the MBT stage of zebrafish embryos (~ 3.5 hpf) using a 44K custom designed chip from Agilent (3 and 4 replicates, respectively). Genes of interest were extracted and evaluated according to expression dynamics and levels.
2010-05-14 | E-GEOD-20137 | biostudies-arrayexpress
Project description:Genome-wide mapping of transcriptional regulatory elements are essential tools for the understanding of the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of nascent, Pol-II-transcribed RNAs by Cap Analysis of Gene Expression (CAGE-Seq) with genome-wide profiling of histones modifications by chromatin immunoprecipitation (ChIP-seq) to map active promoters and enhancers in a model of human neural commitment, represented by embryonic stem cells (ESCs) induced to differentiate into self-renewing neuroepithelial-like stem cells (NESC). We integrated CAGE-seq, ChIP-seq and gene expression profiles to discover shared or cell-specific regulatory elements, transcription start sites and transcripts associated to the transition from pluripotent to neural-restricted stem cell. Our analysis showed that >90% of the promoters are in common between the two cell types, while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a “bivalent” histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provide a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and gene expression programs occurring in the transition from a pluripotent to a neural-restricted cell fate. Genome-wide mapping of H3K4me1 and H3K4me3 in NESCs ChIP-seq for H3K4me1 and H3K4me3 in NESCs
2015-05-21 | E-GEOD-61265 | biostudies-arrayexpress
Project description:Background: Previously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT and early stages of transformation. Results: Genome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA methylation (DNAMe) was applied on a prostate cell model during EMT and malignant transformation. Integrated analyses of promoter epigenetic modifications and gene expression changes revealed strong correlations between the dynamic changes of histone methylations and gene expression. DNA methylation was weakly associated with global gene repression, but strongly correlated to gene silencing when genes co-modified by H3K4me3 were excluded. In genes labeled with multiple epigenetic marks in their promoters, the level of transcription was associated with the net signal intensity of the activating mark H3K4me3 minus the repressive mark H3K27me3 or DNAMe, indicating that the effect on gene expression of bivalent marks (H3K4/K27me3 or H3K4me3/DNAMe) depends on relative modification intensities. Sets of genes, including epithelial cell junction and EMT associated fibroblast growth factor receptor genes, showed corresponding changes concerning epigenetic modifications and gene expression during EMT. Conclusions: This work presents the first blueprint of epigenetic modifications during EMT in prostate cells and shows that specific histone methylations are extensively involved in gene expression reprogramming during EMT and carcinogenesis. The observation that transcription activity of bivalently marked genes depends on the relative labeling intensity of individual marks provides a new view of quantitative regulation of epigenetic modification.
2010-06-09 | E-TABM-983 | biostudies-arrayexpress
Project description:Background: Previously we reported extensive gene expression reprogramming during epithelial to mesenchymal transition (EMT) of primary prostate cells. Here we investigated the hypothesis that specific histone and DNA methylations are involved in coordination of gene expression during EMT and early stages of transformation. Results: Genome-wide profiling of histone methylations (H3K4me3 and H3K27me3) and DNA methylation (DNAMe) was applied on a prostate cell model during EMT and malignant transformation. Integrated analyses of promoter epigenetic modifications and gene expression changes revealed strong correlations between the dynamic changes of histone methylations and gene expression. DNA methylation was weakly associated with global gene repression, but strongly correlated to gene silencing when genes co-modified by H3K4me3 were excluded. In genes labeled with multiple epigenetic marks in their promoters, the level of transcription was associated with the net signal intensity of the activating mark H3K4me3 minus the repressive mark H3K27me3 or DNAMe, indicating that the effect on gene expression of bivalent marks (H3K4/K27me3 or H3K4me3/DNAMe) depends on relative modification intensities. Sets of genes, including epithelial cell junction and EMT associated fibroblast growth factor receptor genes, showed corresponding changes concerning epigenetic modifications and gene expression during EMT. Conclusions: This work presents the first blueprint of epigenetic modifications during EMT in prostate cells and shows that specific histone methylations are extensively involved in gene expression reprogramming during EMT and carcinogenesis. The observation that transcription activity of bivalently marked genes depends on the relative labeling intensity of individual marks provides a new view of quantitative regulation of epigenetic modification.
2010-06-09 | E-TABM-982 | biostudies-arrayexpress
Project description:Very little is known on the nature of epigenetic states in developing zebrafish despite its growing importance as a model organism in developmental biology. We report histone modifications on promoters of pluripotency genes in zebrafish embryos at the mid-late blastula transition (MBT+) stage. We identify three classes of expressed genes based on these profiles: (1) those with a promoter occupied by marks of active genes without any repressive marks; (2) those co-occupied by both activating and repressive modifications; of these genes, klf4 was notably found to be mosaically expressed in the embryo, possibly accounting for this epigenetic pattern; (3) those occupied by repressive marks with, surprisingly, little not acetylated H3K9 or H4. Culture of embryo-derived cells results in a switch from histone acetylation to K9 and K27 trimethylation on genes transcriptionally inactivated, resulting in a profile similar to that of fibroblasts. All promoters retain H3K4me3, indicating no correlation between H3K4me3 occupancy and gene expression. Our results illustrate a complex chromatin state on the promoter of pluripotency-associated genes in the zebrafish embryo, shortly after the embryonic genome is turned on.
2010-02-03 | GSE20137 | GEO