Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Monocyte-to-macrophage differentiation is defined by gain and loss of DNA methylation at transcription factor binding sites

ABSTRACT: Macrophages and their precursors monocytes play a key role in inflammation and chronic inflammatory disorders. Monocyte-to-macrophage differentiation and activation programs are accompanied by significant epigenetic remodeling where DNA methylation associates with cell development and identity. Here we show that confined local gain and loss of DNA methylation at transcription factor binding sites as a key characteristic of macrophage identity. Using the Illumina 450k array with a paired epigenome-wide analysis in combination with public whole-genome sequencing data we found that differential DNA methylation was typically highly localized to single CpGs or very short regions that are enriched for lineage specific enhancers. Furthermore, differentially methylated CpGs were located at sites characterized by increased binding of transcription factors known to be involved in monocyte-to-macrophage differentiation including C/EBP and ETS for gain and AP-1 for loss-of-methylation. Our study highlights subtle, highly localized remodeling of DNA methylation at regulatory regions as key in understanding cell differentiation and, potentially, disease mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118696 | GEO | 2019/08/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ZBTB2 as a novel reader for unmethylated DNA

Project description:In this study, we investigated the dynamics during differentiation of the in vivo binding sites of ZBTB2, a putative reader for unmethylated DNA. We performed DNA pull-downs followed by mass spectrometry, using a genomic sequence containing either unmethylated or methylated CpGs, to study the influence of DNA methylation on ZBTB2 binding. Additionally, we performed interaction proteomics to identify ZBTB2 interaction partners. We found that ZBTB2 recruits a zinc finger module of three proteins to unmethylated DNA.

2018-01-29 | PXD007099 | Pride

CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors

Project description:The DNA hypomethylating drug decitabine maintains normal hematopoietic stem and progenitor cell (HSPC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. To better understand the basis for this contrasting treatment effect, the baseline expression of key lineage-specifying transcription factor (TF) (eg., CEBPa) and key late differentiation TF (CEBPe), was examined in normal, myelodysplastic (MDS) and AML primary cells and cell lines. To appreciate the role of differentiation in hypomethylation of some CpG by decitabine treatment but not others, promoter CpGs, analyzed by microarray and mass spectrometry, were categorized by the direction of methylation change during normal myeloid differentiation. In MDS/AML cells, high expression of CEBPa, relatively low expression of CEBPe (a gene target of CEBPa), hypermethylation of CEBPe promoter CpG, and the methylation pattern at differentiation sensitive promoter CpGs analyzed by microarray, suggested lineage-commitment and aberrant epigenetic repression of late differentiation genes. DNA hypomethylation in response to decitabine was greatest at CpGs that are hypomethylated during normal myeloid differentiation. In contrast, normal HSPC treated with decitabine retained immature morphology, and methylation significantly decreased at CpG that are hypermethylated during myeloid differentiation. Partial differentiation at baseline, and repression of key late differentiation genes by epigenetic means, likely plays a role in methylation and phenotype responses of AML cells treated with decitabine. Bisulphite converted DNA from the 208 samples were hybridised to the Illumina Cancel Panel 1 GPL9183 methylation assay

2011-07-01 | E-GEOD-29047 | biostudies-arrayexpress

Hypoxia Sensing in Resident Cardiac Macrophages Regulates Monocyte Fate Specification following Ischemic Heart Injury

Project description:Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. The mechanisms and dynamics of monocyte differentiation within this context are unknown. We investigated the role of macrophage hypoxia sensing on monocyte differentiation following reperfused myocardial infarction. We show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of a macrophage subset marked by arginase 1 (Arg1) expression. Arg1+ macrophages displayed an inflammatory gene signature and were predicted to represent an intermediate state within the monocyte differentiation cascade. Lineage tracing of Arg1+ macrophages revealed the existence of a monocyte differentiation trajectory consisting of multiple transcriptionally distinct macrophage states. We further showed that deletion of Hif1α in resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1+ trajectory also results in increased heart remodeling following ischemic injury, likely due to the beneficial effects of macrophages downstream of Arg1+ macrophage differentiation. Collectively, our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction.

2024-09-02 | GSE251991 | GEO

Purinergic Preconditioning Induces Epigenomic and Transcriptomic Changes Resembling Epilepsy-associated Microglial States

Project description:DNA methylation profiling of monocytes and monocyte-derived microglia like cells. Innate immune memory was explored in microglia-like cells through consecutive exposure to ATP and LPS.The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

2024-07-09 | GSE235104 | GEO

DNA methylation dynamics during monocyte-to-macrophage differentiation and BCG vaccine induced trained immunity

Project description:DNA methylation dynamics during monocyte-to-macrophage differentiation and BCG vaccine induced trained immunity

| PRJNA713305 | ENA

CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors

2011-07-01 | GSE29047 | GEO

Cell surface mapping and monitoring of cell surface dynamics

Project description:Here, we present a simple and robust N-linked glycoproteome enrichment protocol optimized for deep coverage of the plasma membrane proteome. The procedure was applied to characterize the cell surface proteome of 15 standard laboratory human cell lines and three primary cell types. We observed significant differences in receptor diversity and transporter abundances between primary cells and corresponding cell lines. Relative quantification using isobaric mass tagging enabled quantitative monitoring of dynamic processes on the cell surface in multiplexed experiments. We for the first time report a comprehensive analysis of the profound remodeling of the plasma membrane proteome during monocyte to macrophage differentiation of THP-1 cells. Treatment of these cells with the kinase inhibitor dasatinib (Sprycel) during differentiation severely compromised macrophage differentiation due to an off-target activity resulting in substantial morphological and functional changes and the loss of many macrophage-associated proteins.

2017-03-27 | PXD005846 | Pride

Gene Expression by RNA-Seq of Peripheral Blood Monocyte with the EZH2 inhibitor GSK-343

Project description:Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative M2-like macrophage (M2) polarization, essential for cardiac repair after Myocardial Infarction (MI). We hypothesized that EZH2, responsible for H3K27 methylation, could act as an epigenetic checkpoint regulator during this process. We demonstrate for the first time inactivation of EZH2 activity, linked to ectopic cytoplasmic localization of the epigenetic enzyme, during monocyte differentiation in vitro as well as in M2 macrophages in vivo during post-MI cardiac inflammation. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, resolves H3K27 methylation at the promoter of bivalent genes, thus enhancing their expression to promote human monocyte repair functions. In line with this protective effect, GSK-343 treatment accelerated cardiac inflammatory resolution preventing infarct expansion and subsequent cardiac dysfunction after MI in vivo. In conclusion, our study reveals that epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI.

2023-04-24 | GSE165543 | GEO

Gene expression analyses in IRF8-induced monocyte differentiation

Project description:To understand the differentiation program in monocyte/macrophage differentiation, we performed ChIP-seq for IRF8 and H3K4me1 together with gene expression profiling during IRF8-induced monocyte differentiation. Both promoter-proximal and -distal binding of IRF8 associated with induction of the genes especially those related to monocytes/macrophages and immunity. DNA motif analysis for cis-regulatory elements of indirect IRF8 target genes predicted KLF4, essential for Ly6C+ monocyte development, to be a downstream transcription factor regulating the indirect target gene expression. Introduction of KLF4 into an Irf8-/- myeloid progenitor cell line induced a subset of IRF8 target genes and partially induced monocyte/macrophage differentiation. Together, this study revealed the genome-wide behavior of IRF8 and the IRF8-KLF4 axis during monocyte differentiation. Gene expressions in monocyte-like cells differentiated by IRF8 or KLF4 were measured at day 4 after retroviral transductions to myeloid progenitor cell line, Tot2. Two independent experiments were performed.

2013-01-24 | E-GEOD-38810 | biostudies-arrayexpress

Characterisation of DNA methylation during mesenchymal stem cell chondrogenesis

Project description:Regulation of transcription occurs in a cell type specific manner orchestrated by epigenetic mechanisms including DNA methylation. Methylation changes may also play a key role in lineage specification during stem cell differentiation. To further our understanding of epigenetic regulation in chondrocytes we characterised DNA methylation changes during chondrogenesis of mesenchymal stem cells (MSCs) by Infinium 450K methylation array. Significant DNA hypomethylation was identified during chondrogenesic differentiation including changes at many key cartilage gene loci. Integration with chondrogenesis gene expression data revealed an enrichment of significant CpGs in upregulated genes, while characterisation of significant CpG loci indicated their predominant localisation to enhancer regions. Comparison with methylation profiles of other tissues, including healthy and diseased adult cartilage, identified chondrocyte-specific regions of hypomethylation and the overlap with differentially methylated CpGs in osteoarthritis. Taken together we have associated DNA methylation levels with the chondrocyte phenotype. The consequences of which has potential to improve cartilage generation for tissue engineering purposes and also to provide context for observed methylation changes in cartilage diseases such as osteoarthritis

2019-05-24 | GSE129266 | 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