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Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects

ABSTRACT: Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects

PROVIDER: PRJNA992435 | ENA |

REPOSITORIES: ENA

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Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snhmCseq]

Project description:Oxidative modification of 5-methylcytosine (5mC) by TET DNA dioxygenases generates 5-hydroxymethylcytosine (5hmC), the most abundant form of oxidized 5mC. Existing single-cell bisulfite sequencing methods cannot resolve 5mC and 5hmC, leaving the cell-type-specific regulatory mechanisms of TET and 5hmC largely unknown. Here we present Joint single-nucleus (hydroxy)methylcytosine sequencing (Joint-snhmC-seq), a scalable and quantitative approach that simultaneously profiles 5hmC and true 5mC in single cells by harnessing differential deaminase activity of APOBEC3A towards 5mC and chemically protected 5hmC. Joint-snhmC-seq profiling of single nuclei from the mouse brains reveals an unprecedented level of epigenetic heterogeneity of both 5hmC and true 5mC at single-cell resolution. We show that cell-type-specific profiles of 5hmC or true 5mC improve multi-modal single-cell data integration, enable accurate identification of neuronal subtypes, and uncover context-specific regulatory effects of cell-type-specific genes by TET enzymes.

2023-07-14 | GSE236776 | GEO

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snRNAseq]

2023-07-14 | GSE236769 | GEO

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snmCseq2.split]

2023-07-14 | GSE236789 | GEO

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snhmCseq2.split]

2023-07-14 | GSE236784 | GEO

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snhmCseq]

Project description:Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snhmCseq]

| PRJNA992415 | ENA

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snRNAseq]

Project description:Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [snRNAseq]

| PRJNA992409 | ENA

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snhmCseq2.split]

Project description:Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snhmCseq2.split]

| PRJNA992426 | ENA

Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snmCseq2.split]

Project description:Joint single-cell profiling resolves 5mC and 5hmC and reveals their distinct gene regulatory effects [Joint-snhmC-seq: snmCseq2.split]

| PRJNA992433 | ENA

Methylome of 5mC and 5hmC regulated by NEIL2

Project description:To elucidate the role of DNA glycosylase NEIL2 in regulation of DNA methylome, we performed genome sequencing of epigenetic marker 5mC and 5hmC in genome-wide using enyme-based library methods of TAPS and CAPS. The 5mC and 5hmC profile in CpG contect was further extracted and analysed.

2023-12-13 | GSE240177 | GEO

Control of 5mC and 5hmC by TET dioxygenases in human embryonic carcinoma cells [Microarray]

Project description:The TET family of dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), but their involvement in establishing normal 5mC patterns during mammalian development and their contributions to aberrant control of 5mC during cellular transformation remains largely unknown. We depleted TET1, TET2, and TET3 by siRNA in a pluripotent embryonic carcinoma cell model and examined the impact on genome-wide 5mC and 5hmC patterns. TET1 depletion yielded widespread reduction of 5hmC, while depletion of TET2 and TET3 reduced 5hmC at a subset of TET1 targets suggesting functional co-dependence. TET2 or TET3-depletion also caused increased 5hmC, suggesting they play a major role in 5hmC removal. All TETs prevent hypermethylation throughout the genome, a finding dramatically illustrated in CpG island shores, where TET depletion resulted in prolific hypermethylation. Surprisingly, TETs also promote methylation, as hypomethylation was associated with 5hmC reduction. TET function was highly specific to chromatin environment: 5hmC maintenance by all TETs occurred at polycomb-marked chromatin and genes expressed at moderate levels; 5hmC removal by TET2 is associated with highly transcribed genes enriched for H3K4me3 and H3K36me3. Importantly, genes prone to hypermethylation in cancer become depleted of 5hmC with TET deficiency, suggesting the TETs normally promote 5hmC at these loci, and all three TETs are required for 5hmC enrichment at enhancers, a condition necessary for expression of adjacent genes. These results provide novel insight into the division of labor among TET proteins and reveal an important connection of TET activity with chromatin landscape and gene expression. Affymetrix gene expression Human ST1.0 microarray of NCCIT human embryonic carcinoma cells (4 samples in duplicate).

2014-06-14 | E-GEOD-51901 | biostudies-arrayexpress

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