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Simultaneous profiling of 3D genome structure and DNA methylation in single human cells

ABSTRACT: Simultaneous profiling of 3D genome structure and DNA methylation in single human cells

PROVIDER: PRJNA541105 | ENA |

REPOSITORIES: ENA

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Simultaneous profiling of 3D genome structure and DNA methylation in single human cells

Project description:Dynamic 3D chromatin conformation is a critical mechanism for gene regulation during development and disease. Despite this, profiling of 3D genome structure from complex tissues with cell-type specific resolution remains challenging. Recent efforts have demonstrated that cell-type specific epigenomic features can be resolved in complex tissues using single-cell assays. However, it remains unclear whether single-cell Chromatin Conformation Capture (3C) or Hi-C profiles can effectively identify cell types and reconstruct cell-type specific chromatin conformation maps. To address these challenges, we have developed single-nucleus methyl-3C sequencing (sn-m3C-seq) to capture chromatin organization and DNA methylation information and robustly separate heterogeneous cell types. Applying this method to >4,200 single human brain prefrontal cortex cells, we reconstruct cell-type specific chromatin conformation maps from 14 cortical cell types. These datasets reveal the genome-wide association between cell-type specific chromatin conformation and differential DNA methylation, suggesting pervasive interactions between epigenetic processes regulating gene expression.

2019-09-09 | GSE130711 | GEO

Simultaneous profiling of 3D genome structure and DNA methylation in single human cells.

Project description:Dynamic three-dimensional chromatin conformation is a critical mechanism for gene regulation during development and disease. Despite this, profiling of three-dimensional genome structure from complex tissues with cell-type specific resolution remains challenging. Recent efforts have demonstrated that cell-type specific epigenomic features can be resolved in complex tissues using single-cell assays. However, it remains unclear whether single-cell chromatin conformation capture (3C) or Hi-C profiles can effectively identify cell types and reconstruct cell-type specific chromatin conformation maps. To address these challenges, we have developed single-nucleus methyl-3C sequencing to capture chromatin organization and DNA methylation information and robustly separate heterogeneous cell types. Applying this method to >4,200 single human brain prefrontal cortex cells, we reconstruct cell-type specific chromatin conformation maps from 14 cortical cell types. These datasets reveal the genome-wide association between cell-type specific chromatin conformation and differential DNA methylation, suggesting pervasive interactions between epigenetic processes regulating gene expression.

| S-EPMC6765423 | biostudies-literature

3D chromatin structure in colon cancer

Project description:We report the application of in situ Hi-C technology to 40 colorectal cancer patients and 10 paired-normal tissue to identify CRC specific changes in 3D chromatin structure. The chromatin contact matrices were generated by the sequencing data and image processing/deep learning-based algorithm was proposed to identify long-range abnormal chromatin interaction patterns in the contact matrices. The tumor specific 3D chromatin structure changes and the enhancer-promoter rewiring mediated by the identified chromatin structure changes were analyzed. The complex chromosome-wide rearrangements such as chromothripsis and its effect to 3D chromatin structure were also observed.

2023-07-27 | GSE137188 | GEO

3D genome organisation in Yeast with or without induced DNA methylation

Project description:Effect of induced Methylation on 3D genome organisation in yeast. Hi-C experiment were performed on yeast expressing or not the 4 murine DNMTs (DNMT1, 3a, 3b and 3L).

2020-09-30 | E-MTAB-9257 | biostudies-arrayexpress

KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure

Project description:Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation, such as Pax6. Combination analysis employing ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers. And changes of chromatin structure upregulated expression of neural differentiation-associated genes and promoted early neural differentiation. This study reveals that KLF4 has a differentiation inhibitory effect in regulating 3D chromatin structure and suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.

2022-06-01 | GSE194068 | GEO

Simultaneous detection of chromatin accessibility and DNA methylation in cell cycle

Project description:The goal of this study is to comprehensively assess chromatin accessibility and DNA methylation dynamic in different cell cycle phases, we found DNA methylation is stable in different phases wherase chromatin accessibility underwent enormous changes, but local structure at NDR and NSR are well preserved to maintain cellular identity.

2017-11-09 | GSE89708 | GEO

Dynamic alterations of 3D chromatin structure during differentiation

Project description:Dynamic alterations of 3D chromatin structure during differentiation

| PRJEB4939 | ENA

O-GlcNAcylation of CTCF regulates 3D chromatin structure

Project description:O-GlcNAcylation of CTCF regulates 3D chromatin structure

| PRJNA854623 | ENA

3D Chromosome Structure Can Reveal Stem Cell Signatures

Project description:3D Chromosome Structure Can Reveal Stem Cell Signatures

| PRJNA518890 | ENA

Simultaneous single-cell three-dimensional genome and gene expression profiling Uncovers Dynamic Enhancer Connectivity Underlying Olfactory Receptor Choice [scATAC-Seq, scRNA-seq]

Project description:The simultaneous measurement of three-dimensional (3D) genome structure and gene expression of individual cells is critical for understanding our genome’s structure–function relation, yet is extremely challenging for existing methods. Here we present Linking mRNA to Chromatin Architecture (LiMCA), which jointly profiles 3D genome and transcriptome with exceptional sensitivity and from low-input materials. Combining LiMCA and our high-resolution scATAC-seq assay, METATAC, we profiled the developing mouse olfactory epithelium and reported the first chromatin accessibility profiles and the first paired 3D genome structures and gene expression information of single neurons. We greatly expanded the repertoire of known OR enhancers, and discovered unexpected rules of their dynamics: ORs and their enhancers are most accessible during early differentiation, and the active OR typically does not associate with the largest enhancer hub. These findings offer valuable insights into how 3D connectivity of ORs and enhancers dynamically orchestrate the “one neuron–one receptor” selection process.

2024-01-15 | GSE239876 | GEO

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