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Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution.

ABSTRACT: Long-range interactions between regulatory elements and promoters are key in gene transcriptional control; however, their study requires large amounts of starting material, which is not compatible with clinical scenarios nor the study of rare cell populations. Here we introduce low input capture Hi-C (liCHi-C), as a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. As a proof of its broad applicability, we implement liCHi-C to study normal and malignant human hematopoietic hierarchy in clinical samples. We demonstrate that the dynamic promoter architecture identifies developmental trajectories and orchestrates transcriptional transitions during cell-state commitment. Moreover, liCHi-C enables the identification of new disease-relevant cell types, genes and pathways potentially deregulated by non-coding alterations at distal regulatory elements. Finally, we show that liCHi-C can be harnessed to uncover genome-wide structural variants, resolve their breakpoints and infer their pathogenic effects. Collectively, our optimized liCHi-C method expands the study of 3D chromatin organization to unique, low-abundance cell populations, and offers an opportunity to uncover novel factors and regulatory networks involved in disease pathogenesis.

PROVIDER: EGAS00001006305 | EGA |

REPOSITORIES: EGA

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3D genome organization during TGFB-induced transcription requires nuclear microRNA and G-quadruplexes

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2024-07-30 | MSV000095480 | MassIVE

ChIP-seq analysis of Gli1 and Sox2 input to neural progenitor program and integration with actve histone marks

Project description:In the vertebrate neural tube, regional Sonic hedgehog (Shh) signaling invokes a time- and concentration-dependent induction of six different cell populations mediated through Gli transcriptional regulators. Elsewhere in the embryo, Shh/Gli responses invoke different tissue appropriate regulatory programs. To elucidate Shh/Gli regulation of neural fate sepcification, we performed Gli1 ChIP-Seq analysis. We further analyzed two transcription factors whose motifs were enriched in Gli1 ChIP data (Sox2 and Foxa2). Two active histone marks (H3K4me2 and H3K27ac) were additionally analyzed to study activity status of Shh-responsive cis-elements. Active enhancer histone marks and transcription factor binding patterns were obtained from neuralized emrbyoid bodies. Biological replicates were performed for Gli1 and mock FLAG chips. Histone profiling for enhancer marks were taken from time course experiment performed in parallel.

2012-12-15 | E-GEOD-42132 | biostudies-arrayexpress

ChIP-seq analysis of Gli1 and Sox2 input to neural progenitor program and integration with actve histone marks

2012-12-15 | GSE42132 | GEO

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Project description:Genome organisation determines chromosome interactions between regulatory elements, such as promoters and enhancers, influencing gene expression. Despite the fact that it is possible to assess whether a gene is actively transcribed, it has been challenging to point out the genomic regions that are involved in the regulation of a particular gene. We are interested in better understanding the interactions between promoters and their regulatory elements in colorectal cancer in order to unveil novel non-coding regions which might have a role in tumour development. To do so, we utilise the HiC method complemented with promoter capture in combination with NGS to map promoter interactions in two CRC cell lines, representing two distinct CRC subtypes.

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2020-12-14 | PXD022088 | Pride

FIREWACh: High-throughput Functional Detection of Transcriptional Regulatory Modules in Mammalian Cells

2014-03-22 | GSE54863 | GEO

Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells

Project description:Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression. It is a mystery how chromatin marks in regulatory elements are modulated to establish cell type-specific gene expression. Here we profiled a variety of epigenetic marks in the regulatory elements using massive ChIP-seq (n=84). We uncovered two classes of regulatory elements: Class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas Class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. For common genes regulated by both promoters and enhancers, Class I promoters displayed dominant regulatory effects on transcriptional abundance. Moreover, human iPSCs and somatic cells selected their preferential regulatory elements to maintain cell type-specific gene expression. Our study provides valuable resources for deciphering the epigenetic modulation of regulatory elements that fine-tune spatiotemporal gene expression in human development and diseases.

2017-12-04 | GSE97033 | GEO

FIREWACh: High-throughput Functional Detection of Transcriptional Regulatory Modules in Mammalian Cells

Project description:We report a new method called FIREWACh (Functional Identification of Regulatory Elements Within Accessible Chromatin), a high-throughput functional assay for directly identifying active promoter and enhancer elements. FIREWACh simultaneously assessed over 80,000 DNA fragments derived from M-bM-^@M-^\nucleosome-free regionsM-bM-^@M-^] within embryonic stem cell (ESC) chromatin to identify 6,364 new active regulatory elements. Many FIREWACh DNAs represent newly discovered ESC-specific enhancers and their analyses identified enriched binding site motifs for ESC transcription factors including SOX2, POU5f1 (OCT4), and KLF4. Thus FIREWACh identifies endogenous regulators of gene expression and can be used for the discovery of key cell-specific transcription factors. The application of FIREWACh to additional cultured cell types will facilitate functional annotation of the genome and expand our view of transcriptional network dynamics. Nucleosome free DNA (i.e. "open chromatin") is isolated enzymatically from cross-linked nuclei of cells (e.g. mouse embryonic stem cells, mESC) and cloned upstream of a minimal promoter driving GFP within a lentivral reporter construct. Virus is made from a pooled library of these plasmids, and used to transfect the target cell (mESC). GFP positive cells contain active NFRs and can be sorted by FACS. The loci of the NFR is determined using high throughput sequencing and mapping.

2014-03-22 | E-GEOD-54863 | biostudies-arrayexpress

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