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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos.

ABSTRACT: Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos.

PROVIDER: PRJNA677885 | ENA |

REPOSITORIES: ENA

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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]

Project description:Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]

| PRJNA677891 | ENA

Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]

Project description:Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]

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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos.

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-12 | GSE161328 | GEO

Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]

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.

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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]

2021-12-12 | GSE161326 | GEO

Data for: A practical guide for analysis of histone post-translational modifications by mass spectrometry: best practices and pitfalls

Project description:Histone proteomics from 5 human cell lines, discussed in publication: "A practical guide for analysis of histone post-translational modifications by mass spectrometry: best practices and pitfalls". Further explanation of data types, methods, and analysis are available in Data Explanation document in the Methods and Protocols folder.

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Chromatin architecture landscape in hierarchical hematopoietic cells

Project description:Chromatin architecture landscape in hierarchical hematopoietic cells

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sox32 Alleles Generated from Four-guide Cas9 RNP Targeting in G0 Zebrafish Embryos

Project description:We report long-read sequencing results from the sox32 allele targeted with a multi-guide Cas9 RNP strategy. Embryos were cell-injected with Cas9 RNP programmed with 4 guides simultaneously targeting different portions of the sox32 gene. Genomic DNA was extracted from each embryo and the sox32 coding sequence and intron were amplified and sequenced. Six individual embryos were evaluated. We found that the majority of sequences were unique and most involved mutations confined to the target sites rather than larger lesions spanning two or more target sites. We also found that alleles accumulated mutations over several DNA replication cycles, which may in part explain the diversity of alleles that were generated. This study is the first to use high-throughput sequencing to evaluate of an allele of this size mutated by a multi-guide Cas9 RNP strategy and provides insights into the dynamics of CRISPR-Cas9 RNP gene editing in vivo.

2018-07-01 | GSE115233 | GEO

A viral guide RNA delivery system for CRISPR-based transcriptional activation and heritable targeted DNA demethylation

Project description:CRISPR-based epigenome editing was recently used to activate gene expression through direct transcriptional activation or site-specific DNA demethylation. Viral delivery of guide RNAs for these purposes remains to be developed. Furthermore, currently available viral delivery tools for genome editing show meager rates of heritability. Here, we have developed a tobacco rattle virus (TRV)-based guide RNA delivery system for both transcriptional activation and targeted DNA demethylation. To promote heritable epigenome editing specifically within plant meristems and the germline, we used the tRNA-guide RNA expression system to express guide RNAs from the viral genome, thus facilitating cell-to-cell movement of the RNA in plants. We achieved up to ~8% heritability of the induced phenotype in the progeny of virus-inoculated plants and 25% in the following generation, indicating high rates of heritability for targeted DNA demethylation. Thus, TRV delivery, in combination with a specific tRNA-gRNA architecture, provides for fast and effective epigenome editing.

2021-02-16 | GSE148934 | GEO

LaminA/C regulates epigenetic and chromatin architecture changes upon aging of hematopoietic stem cells

Project description:The decline of hematopoietic stem cell (HSC) function upon aging contributes to the senescent immune remodeling and to leukemia pathogenesis. Aged HSCs show changes in their epigenome, like alterations in the global and local DNA/histone methylation and histone acetylation landscape. Previously, we showed a correlation between high Cdc42 activity and the loss of intra-nuclear epigenetic polarity (epipolarity), as indicated by the specific location of histone H4 lysine 16 acetylation (H4K16ac). Here, we show that not all histone modifications display a polar localization and that loss of H4K16ac amount and epipolarity is specific to aged HSCs. Increased levels of H4K16ac are insufficient to restore polarity in aged HSCs and for the restoration of HSC function. Changes in H4K16ac upon aging and rejuvenation of HSCs are correlated to a shift of chromosome 11 architecture and nuclear volume and shape. Surprisingly, by taking advantage of knock-out mouse models we demonstrate that increased Cdc42 activity levels correlate with the repression of LaminA/C expression, which control chromosome 11 distribution, H4K16ac polarity and the nuclear volume and shape of aged HSCs. These chromatin and epigenetic architecture changes are targeted by altering the activity of the small RhoGTPase Cdc42, that regulates LaminA/C. Collectively, our data show that chromatin architecture changes in stem cells are reversible by changing levels of Cdc42 activity, revealing an unanticipated way to pharmacologically target LaminA/C expression and revert alterations of the epigenetic architecture in aged HSCs.

2018-09-05 | GSE119466 | GEO

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