Similar Datasets
Project description:The gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development.
| S-EPMC8764075 | biostudies-literature
Project description:We performed multi-omics exploration of early aorta endothelial cells (AECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) along definitive HSC emergence in mouse embryos. Globally, we find that most hematopoiesis related enhancers were already pre-activated at the beginning, followed by strengthened looping structure of enhancers and promoters. After the stronger interactions forming, enhancers can be further activated to promote hematopoiesis gene expressions. Specifically, the important hematopoietic transcription factor (TF) RUNX1 can mediate enhancer-promoter interactions, which starts from a subset of early AECs, prior to appearance of HECs. Thus, the stepwise and asynchrony cooperation of multi-omics and TFs in definitive hematopoiesis has been revealed holistically in vivo. It may also reflect general epigenetic regulation models of developmental processes.
2021-12-12 | GSE161327 | GEO
Project description:We performed multi-omics exploration of early aorta endothelial cells (AECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) along definitive HSC emergence in mouse embryos. Globally, we find that most hematopoiesis related enhancers were already pre-activated at the beginning, followed by strengthened looping structure of enhancers and promoters. After the stronger interactions forming, enhancers can be further activated to promote hematopoiesis gene expressions. Specifically, the important hematopoietic transcription factor (TF) RUNX1 can mediate enhancer-promoter interactions, which starts from a subset of early AECs, prior to appearance of HECs. Thus, the stepwise and asynchrony cooperation of multi-omics and TFs in definitive hematopoiesis has been revealed holistically in vivo. It may also reflect general epigenetic regulation models of developmental processes.
2021-12-12 | GSE161326 | GEO
Project description:Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos.
| PRJNA677885 | ENA
Project description:Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]
| PRJNA677891 | ENA
Project description:Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]
| PRJNA677890 | ENA
Project description:Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.
| S-EPMC3193420 | biostudies-other
Project description:Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the emergence of bivalent chromatin are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions of modifications, and sufficient nonlinearity. The first condition is further confirmed by analyzing the existing experimental data. Investigation of the composition of bivalent chromatin reveals that bivalent nucleosomes carrying both H3K4me3 and H3K27me3 account for no more than half of nucleosomes at the bivalent chromatin domain. We identify that bivalent chromatin not only allows transitions to multiple states but also serves as a stepping stone to facilitate a stepwise transition between repressive chromatin state and activating chromatin state and thus elucidate crucial roles of bivalent chromatin in mediating phenotypical plasticity during cell fate determination.
| S-EPMC8261666 | biostudies-literature
Project description:Every cell has to duplicate its entire genome during S-phase of the cell cycle. After replication, the newly synthesized DNA is rapidly assembled into chromatin. The newly assembled chromatin 'matures' and adopts a variety of different conformations. This differential packaging of DNA plays an important role for the maintenance of gene expression patterns and has to be reliably copied in each cell division. Posttranslational histone modifications are prime candidates for the regulation of the chromatin structure. In order to understand the maintenance of chromatin structures, it is crucial to understand the replication of histone modification patterns. To study the kinetics of histone modifications in vivo, we have pulse-labeled synchronized cells with an isotopically labeled arginine ((15)N(4)) that is 4 Da heavier than the naturally occurring (14)N(4) isoform. As most of the histone synthesis is coupled with replication, the cells were arrested at the G1/S boundary, released into S-phase and simultaneously incubated in the medium containing heavy arginine, thus labeling all newly synthesized proteins. This method allows a comparison of modification patterns on parental versus newly deposited histones. Experiments using various pulse/chase times show that particular modifications have considerably different kinetics until they have acquired a modification pattern indistinguishable from the parental histones.
| S-EPMC2731903 | biostudies-literature
Project description:The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator-histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization.
| S-EPMC3201872 | biostudies-literature