Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo.

ABSTRACT: CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo.

PROVIDER: PRJNA918411 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22974800_1.fastq.gz	Fastqsanger.gz
	SRR22974800_2.fastq.gz	Fastqsanger.gz
	SRR22974801_1.fastq.gz	Fastqsanger.gz
	SRR22974801_2.fastq.gz	Fastqsanger.gz
	SRR22974802_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 276

Similar Datasets

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [methylation array]

Project description:CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [methylation array]

| PRJNA918412 | ENA

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [Targeted BS-seq]

Project description:CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [Targeted BS-seq]

| PRJNA918419 | ENA

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [methylation array]

Project description:Ageing is associated with an abnormal increase of DNA methylation in human gene promoters, including in the bone marrow stem cells. DNA methylation patterns are further perturbed in haematological malignancies such as acute myeloid leukaemia (AML) but the physiological significance of such epigenetic changes is unknown. Using epigenetic editing of human stem/progenitor cells (HSPCs), we show evidence that p15 methylation affects haematopoiesis in vivo. We edited the CDKN2B (p15) promoter and ARF (p14) using dCas9-3A3L and observed DNA methylation spreading beyond the location of the gRNA. We find that despite a transient delivery system, DNA methylation is maintained during myeloid differentiation in vitro, and hypermethylation of the p15 promoter reduces gene expression. In vivo, edited human HSPCs can engraft the bone marrow of mice and targeted DNA methylation is maintained in HSPCs long term. Moreover, we identified how the epigenetic changes are conserved and inherited in both myeloid and lymphoid lineages. Although the proportion of myeloid (CD33+) and lymphoid (CD19+) cells is unaffected, monocyte (CD14+) populations decreased and granulocytes (CD66b+) increased in mice engrafted with p15 hypermethylated cells. We also observe significant changes in the proportions of multipotent and committed progenitor cells. This may have clinical relevance since we found that p15 promoter methylation is present in the peripheral blood of patients with clonal haematopoiesis. Our study shows DNA methylation can be targeted and maintained in human HSPCs and demonstrated functional relevance of aberrant DNA methylation on the p15 locus. As such, other ageing associated aberrant DNA methylation may impact haematopoiesis in vivo.

2023-08-30 | GSE222178 | GEO

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo [Targeted BS-seq]

2023-08-30 | GSE222179 | GEO

CRISPR/dCas9 DNA methylation editing is heritable during human haematopoiesis and can impair differentiation in vivo.

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

2023-08-30 | GSE222181 | GEO

CRISPR/dCas9 DNA methylation editing is heritable during human hematopoiesis and shapes immune progeny [RNA-seq]

Project description:CRISPR/dCas9 DNA methylation editing is heritable during human hematopoiesis and shapes immune progeny [RNA-seq]

| PRJNA981091 | ENA

CUT&RUN-seq of H3K9me3, H4K20me3 or H3K4me3 in mESC after epigenetic editing and upon release of the trigger

Project description:Enrichment of histone marks was assessed by CUT&RUN-sequencing after epigenetic editing with dCas9::KRAB (or dCas9::GFP as a control) and subsequently upon release of the trigger. Samples were collected after 7 days of DOX induction (epigenetic editing) and after 4 and 7 days of DOX washout (release of the trigger).

2021-11-23 | E-MTAB-10525 | biostudies-arrayexpress

Epigenome editing strategies for the functional annotation of topological insulators

Project description:The human genome is folded into regulatory units termed ‘topologically-associated domains’ (TADs), within which the majority of gene-enhancer interactions occur. Genome-wide studies support a global role for the insulator protein CTCF in mediating chromosomal looping and the topological constraint of TAD boundaries3,4. However, the impact of individual insulators on enhancer-gene interactions and transcription remains poorly understood. Here, we investigate epigenome editing strategies for perturbing individual CTCF insulators and evaluating consequent effects on genome topology and transcription. We show that fusions of catalytically-inactive Cas9 (dCas9) to transcriptional repressors (dCas9-KRAB) and DNA methyltransferases (dCas9-DNMT3A, dCas9-DNMT3A3L) can selectively displace CTCF from specific insulators, but only when precisely targeted to the cognate motif. We further demonstrate that stable, mitotically-heritable insulator disruption can be achieved through combinatorial hit-and-run epigenome editing with dCas9-KRAB and dCas9-DNMT3A3L. Finally, we apply these strategies to activate PDGFRA expression in glioblastoma stem cells, thus simulating an insulator loss mechanism implicated in brain tumorigenesis. Our study provides strategies for stably modifying genome organization and gene activity without altering the underlying DNA sequence.

2019-08-07 | GSE121998 | GEO

ATAC-seq of ESC or in vitro differentiated endoderm cells after epigenetic editing and upon release of the trigger

Project description:Chromatin accessibility was assayed in ESC after epigenetic editing with dCas9::KRAB (or dCas9::GFP as a control) and subsequently in ESC and Endoderm differentiated cells upon release of the trigger. Samples were collected in two biological replicates after 7 days of DOX induction in ESC (epigenetic editing) and after 7 days of DOX washout (release of the trigger) in ESC and Endoderm cells.

2021-11-23 | E-MTAB-10523 | biostudies-arrayexpress

Chem-CRISPR/dCas9 -a chemically induced platform for epigenome editing

Project description:Epigenetic aberration is one of the major driving factors in the initiation, promotion, and progression of human cancer and it is also often associated with acquired therapeutic resistance. Several chemical epigenetic modulators have been reported. However, results from animal models and clinical trials have indicated that severe on- and off-target toxicity is one of the leading factors behind failures in epidrug development. CRISPR/dCas9 technology provides a powerful tool for precise epigenetic regulation at the single-gene level. This approach requires ectopic expression of exogenous epigenetic modulatory proteins, which cause side effects and technical challenges for preparation and delivery. Recently, we have shown that Cas9 tagging with the peptide motif (FCPF) was recognized by perfluoro biphenyl derivatives. Here, we introduced the FCPF-tag into dCas9 and report a chemically induced platform for epigenome editing (Chem-CRISPR/dCas9FCPF). By conjugating JQ1, a BRD4 inhibitor, to perfluoro biphenyl (JQ1-FCPF), we demonstrate that JQ1-FCPF covalently binds to CRISPR/dCas9 and specifically inhibits BRD4 in proximity to the promoters/enhancers of c-MYC with the guidance of c-MYC sgRNAs. Thus, we achieved epigenetic modulation of c-MYC with high efficiency and specificity.

2023-06-09 | GSE232132 | GEO

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