Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hierarchical chromatin regulation during blood formation uncovered by single-cell sortChIC

ABSTRACT: Post-translational histone modifications modulate chromatin packing to regulate gene expression. How chromatin states, both at euchromatic and at heterochromatic regions, underlie cell fate decisions in single cells is relatively unexplored. We develop sort assisted single-cell chromatin immunocleavage (sortChIC) and apply it to map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in hematopoietic stem and progenitor cells (HSPCs), and mature blood cells in the mouse bone marrow. During differentiation, HSPCs acquire distinct active chromatin states that depend on the specific cell fate, mediated by cell type-specifying transcription factors. By contrast, most regions that gain or lose repressive marks during differentiation do so independent of the specific cell fate. Joint profiling of active H3K4me1 and repressive H3K9me3 in single cells demonstrates that cell types within the myeloid lineage have distinct active chromatin regulation but share a similar myeloid-specific heterochromatin-repressed state. Our results suggest a hierarchical chromatin regulation program during hematopoiesis, by which heterochromatin dynamics define differentiation trajectories and lineages, while euchromatin dynamics establish cell types within lineages.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE164779 | GEO | 2021/11/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

scChIX-seq infers dynamic relationships between histone modifications in single cells

Project description:Regulation of chromatin states involves the dynamic interplay between different histone modifications to control gene expression. Recent advances have enabled mapping of histone marks in single cells, but most methods are constrained to profile only one histone mark per cell. Here we present an integrated experimental and computational framework, scChIX-seq (single-cell chromatin immunocleavage and unmixing), to map multiple histone marks in single cells. scChIX-seq multiplexes two histone marks together in single cells, then computationally deconvolves the signal using training data from respective histone mark profiles. This framework learns the cell type-specific correlation structure between histone marks, and therefore does not require a priori assumptions of their genomic distributions. Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single cells across a range of mark combinations: two repressive marks, two active marks, and an active plus a repressive mark. In mouse gastrulation, we find that cell type-specific regulation in active chromatin can be accompanied by stable heterochromatin landscapes that are shared across cell types. Applying scChIX-seq to two active marks during macrophage differentiation, we find H3K4me1 dynamics preceding H3K36me3. Modeling these dynamics enables integrated analysis of chromatin velocity during differentiation. Overall, scChIX-seq unlocks systematic interrogation of the interplay between histone modifications in single cells.

2021-11-30 | GSE155280 | GEO

ChIP-seq dataset for epigenomic landscape of MPNST

Project description:In order to comprehensively define the epigenetic patterns specific to MPNST, we generated profiles for 6 histone modification marks, including H3K4me1 (enhancer), H3K27Ac (active enhancer), H3K9me3 (heterochromatin), H3K27me3 (polycomb repression), H3K79me2 (transcription) and H3K4me3 (promoter). Systematic epigenomic profiling of chromatin states in MPNST cells revealed epigenetic subtypes in MPNST based on Polycomb related repressive and bivalent chromatin states. We demonstrate that PRC2 loss led to de-repression and subsequent enhancer reprogramming at key neural crest specifiers aiding the acquisition of this de-differentiated aggressive tumor phenotype.

2021-06-28 | GSE141435 | GEO

The H3K9me3 heterochromatin integrity and function are sustained by H3K9me3 methyltransferases-HP1 dependencies [TT-Seq]

Project description:H3K9me3-heterochromatin, compacted by HP1 proteins, restricts transcription factor binding and functions as a barrier to cell fate changes in development and reprogramming1,2. To investigate principles underlying H3K9me3-heterochromatin maintenance in mammalian cells, we applied degron engineering3,4 on mouse ESCs to conditionally deplete all three H3K9me3-methyltransferases within one hour and found an unexpectedly dynamic nature of heterochromatin maintenance. Following H3K9me3 methyltransferases degradation, HP1β dissociates from heterochromatin within three hours, and transcription factors quickly access the de-compacted heterochromatin, activating transcription of their targets, which then promotes H3K9me3 decay. Both passive dilution and active removal contribute to the H3K9me3 decay. Mathematical modeling reveals distinct H3K9me3 heterochromatin states with diverse chromatin features which influence initial H3K9me3 levels and the stability of H3K9me3 domains, thereby expanding our understanding of distinct heterochromatin domains. Rampant transposable element de-repression interferes with transcription of poised early developmental and signaling genes outside H3K9me3-domains, highlighting the intricate roles of dynamic H3K9me3-heterochromatin maintenance in safeguarding developmental programs. Our findings deconvolve the hierarchical relationships between H3K9me3 marks, methyltransferases, HP1 and transcription factors to reveal principles of H3K9me3-heterochromatin maintenance and how its remodeling enables transcription and cell fate change.

2024-09-19 | GSE233040 | GEO

The H3K9me3 heterochromatin integrity and function are sustained by H3K9me3 methyltransferases-HP1 dependencies [ATAC-Seq]

2024-09-19 | GSE233039 | GEO

The H3K9me3 heterochromatin integrity and function are sustained by H3K9me3 methyltransferases-HP1 dependencies [ChIP-Seq]

2024-09-19 | GSE231845 | GEO

The H3K9me3 heterochromatin integrity and function are sustained by H3K9me3 methyltransferases-HP1 dependencies [H4K20me3 ChIP-seq]

2024-09-19 | GSE270213 | GEO

Histone H3.3 is required for endogenous retroviral element silencing and genome stability [RNA-Seq]

Project description:Endogenous retroviruses (ERVs) have provided an evolutionary advantage in the diversification of transcript regulation and are thought to be involved in the establishment of extraembryonic tissues during development. However, silencing of these elements remains critical for the maintenance of genome stability. Here, we define a new chromatin state that is uniquely characterized by the combination of the histone variant H3.3 and H3K9me3, two chromatin ‘marks’ that have previously been considered to belong to fundamentally opposing chromatin states. H3.3/H3K9me3 heterochromatin is fundamentally distinct from ‘canonical’ H3K9me3 heterochromatin that has been under study for decades and this unique functional interplay of a histone variant and a repressive histone mark is crucial for silencing ERVs in ESCs. Our study solidifies the emerging notion that H3.3 is not a histone variant associated exclusively with “active” chromatin and further suggests that its incorporation at unique heterochromatic regions may be central to its function during development and the maintenance of genome stability. RNA-seq analysis of three embryonic stem cell lines WT, H3.3 KO1, and H3.3 KO2)

2015-05-05 | E-GEOD-59104 | biostudies-arrayexpress

Loss of H3K9 tri-methylation alters mitotic chromosome compaction and transcription factor retention during mitosis

Project description:Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases (DNMTs) and Polycomb Repressor Complexes (PRCs), bind to chromosomes throughout mitosis and their depletion results in increased chromosome size. Enzymes that catalyse H3K9 methylation, such as Suv39h1, Suv39h2, G9a, GLP are also retained by mitotic chromosomes. Surprisingly however, mutants lacking H3K9me3 have unusually small and compact mitotic chromosomes that are associated with increased H3S10ph and H3K27me3 levels. Chromosome size and centromere compaction in these mutants was rescued by providing exogenous Suv39h1, or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wildtype versus Suv39h1,2 double null ESCs revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis, and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.

2022-10-12 | PXD030771 | Pride

Loss of H3K9 tri-methylation alters chromosome compaction and transcription factor retention during mitosis

Project description:Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and Polycomb Repressor Complexes, bind to chromosomes throughout mitosis and their depletion results in increased chromosome size. Here we show that enzymes that catalyse H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly however, mutants lacking H3K9me3 have unusually small and compact mitotic chromosomes associated with increased H3S10ph and H3K27me3 levels. Chromosome size and centromere compaction in these mutants were rescued by providing exogenous Suv39h1, or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wildtype versus Suv39h1/Suv39h2 double-null mouse ESCs revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis, and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.

2023-01-25 | PXD039521 | Pride

Dynamics of de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

Project description:Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here, we discover a checkpoint regulated cascade of chromatin signaling that activates 5 the histone methyltransferase EHMT2/G9a to catalyze heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fiber approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favored by the G9a-dependent exclusion of the H3K9-demethylase 10 JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering ssDNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help explaining chemotherapy resistance and poor prognosis observed in cancer patients displaying elevated level of G9a/H3K9me3.

2023-05-12 | PXD041742 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data