Single Cell RNA-Seq Reveals Changing Landscape of Cell-to-Cell Variation Induced by CTCF Knockdown
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ABSTRACT:
PROVIDER: PRJNA560032 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9960590.fastq.gz | Fastqsanger.gz | |||
| SRR9960600.fastq.gz | Fastqsanger.gz | |||
| SRR9960610.fastq.gz | Fastqsanger.gz | |||
| SRR9960620.fastq.gz | Fastqsanger.gz | |||
| SRR9960630.fastq.gz | Fastqsanger.gz |
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Project description:In this study, we knockdown the expression of CTCF in EL4 cells by shRNA, followed by single cell RNA-seq on both wild type (WT) cells and CTCF-Knockdown (CTCF-KD) cells. Principal component analysis (PCA) of single cell RNA-seq data showed that WT cells and CTCF-KD cells essentially concentrated in two different clusters on the PCA projection, indicating gene expression profiles of CTCF-KD cells and WT cells were systematically different. We further found the cells’ CTCF expression levels were correlated with the cell’s positioning on PCA projection. Interestingly, GO terms including regulation of transcription, DNA binding, Zinc finger and transcription factor binding are significantly enriched in CTCF-KD specific highly variable genes, indicating tissue specific genes such as transcription factors were highly sensitive to CTCF-KD level and showed strongly increased variation. While the housekeeping genes including rRNA processing, DNA repair and tRNA processing are significantly enriched in WT specific highly variable genes, potentially indicating cell-to-cell variation of cell activity in WT cells is higher than that of CTCF-KD cells. We found CTCF-KD cell specific highly variable genes were significantly enriched in CTCF-KD specific down-regulated genes, indicating knockdown of CTCF simultaneously reduced expression levels and increased gene expression noises of its target genes. In summary, analysis of genome-wide cell-to-cell variation in this study showed CTCF-medicated promoter-enhancer interaction not only important for maintaining the expression of its target genes, but also played important roles in reducing the expression noise of its target genes.
2020-01-08 | GSE135769 | GEO
Project description:This study will look at variation in CTCF binding in humans as assayed by ChIP-seq on 60 HapMap lymphoblastoid cell lines.
2013-09-04 | E-ERAD-141 | biostudies-arrayexpress
Project description:BACKGROUND:CCCTC-Binding Factor (CTCF), also known as 11-zinc finger protein, participates in many cellular processes, including insulator activity, transcriptional regulation and organization of chromatin architecture. Based on single cell flow cytometry and single cell RNA-FISH analyses, our previous study showed that deletion of CTCF binding site led to a significantly increase of cellular variation of its target gene. However, the effect of CTCF on genome-wide landscape of cell-to-cell variation remains unclear. RESULTS:We knocked down CTCF in EL4 cells using shRNA, and conducted single cell RNA-seq on both wild type (WT) cells and CTCF-Knockdown (CTCF-KD) cells using Fluidigm C1 system. Principal component analysis of single cell RNA-seq data showed that WT and CTCF-KD cells concentrated in two different clusters on PC1, indicating that gene expression profiles of WT and CTCF-KD cells were systematically different. Interestingly, GO terms including regulation of transcription, DNA binding, zinc finger and transcription factor binding were significantly enriched in CTCF-KD-specific highly variable genes, implying tissue-specific genes such as transcription factors were highly sensitive to CTCF level. The dysregulation of transcription factors potentially explains why knockdown of CTCF leads to systematic change of gene expression. In contrast, housekeeping genes such as rRNA processing, DNA repair and tRNA processing were significantly enriched in WT-specific highly variable genes, potentially due to a higher cellular variation of cell activity in WT cells compared to CTCF-KD cells. We further found that cellular variation-increased genes were significantly enriched in down-regulated genes, indicating CTCF knockdown simultaneously reduced the expression levels and increased the expression noise of its regulated genes. CONCLUSIONS:To our knowledge, this is the first attempt to explore genome-wide landscape of cellular variation after CTCF knockdown. Our study not only advances our understanding of CTCF function in maintaining gene expression and reducing expression noise, but also provides a framework for examining gene function.
| S-EPMC6933653 | biostudies-literature
Project description:Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically-associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers. Deletion of CTCF sites using CRISPR/Cas9 compromises enhancer-promoter interactions. Using single-cell flow cytometry and single-molecule RNA-FISH assays, we demonstrate that knocking down of CTCF or deletion of a CTCF binding site results in increased cell-to-cell variation of gene expression, indicating that long-range promoter-enhancer interaction mediated by CTCF plays an important role in controlling the cell-to-cell variation of gene expression in mammalian cells.
2017-10-01 | GSE66343 | GEO
Project description:Effect of CTCF and Rad21 knockdown on cell and KSHV gene expression
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Project description:SMC1A, CTCF and MITF level on chromatin was studied after knockdown of NIPBL in 501mel
2025-05-01 | GSE263452 | GEO
Project description:Transcriptional profiling of immortalized human prostate epithelial cells after CTCF knockdown by short hairpin RNA. Knockdown by shRNA targeting CTCF was conducted for 5 days by addition of doxycycline to induce shRNA expression. RNA was purified from triplicate biological replicates of induced and uninduced shRNA samples. Gene expression was quantified by hybridization to Affymetrix Human Transciptome 2.0 arrays.
2019-02-20 | GSE93363 | GEO
Project description:SMC1A, CTCF and MITF level on chromatin after knockdown of NIPBL in melanoma cell line
| PRJNA1097574 | ENA
Project description:CTCF and the cohesin complex modify chromatin by binding to DNA and interacting with each other and with other cellular proteins. Both proteins regulate transcription by a variety of local effects on transcription and by long range topological effects. CTCF and cohesin also bind to herpesvirus genomes at specific sites and regulate viral transcription during latent and lytic cycles of replication. Kaposi’s sarcoma-associated herpesvirus (KSHV) transcription is regulated by CTCF and cohesin, with both proteins previously reported to act as restrictive factors for lytic cycle transcription and virion production. In this study, we examined the interdependence of CTCF and cohesin binding to the KSHV genome. ChIP-seq analyses revealed that cohesin binding to the KSHV genome is highly CTCF dependent whereas CTCF binding does not require cohesin. Further, depletion of CTCF leads to almost complete dissociation of cohesin from sites at which they colocalize. Thus, previous studies which examined the effects of CTCF depletion actually represent concomitant depletion of both CTCF and cohesin components. Analysis of the effects of single and combined depletion indicate that CTCF primarily activates KSHV lytic transcription whereas cohesin has primarily inhibitory effects. Further, CTCF or cohesin depletion was found to have regulatory effects on cellular gene expression relevant for control of viral infection, with both proteins potentially facilitating expression of multiple genes important in the innate immune response to viruses. Thus, CTCF and cohesin have both positive and negative effects on KSHV lytic replication as well as effects on the host cell that enhance antiviral defenses.
2019-10-24 | GSE138105 | GEO
Project description:The transcription factor CTCF appears indispensable in defining topologically associated domain boundaries and maintaining chromatin loop structures within these domains, supported by numerous functional studies. However, acute depletion of CTCF globally reduces chromatin interactions but does not significantly alter transcription. Here we systematically integrated multi-omics data including ATAC-seq, RNA-seq, WGBS, Hi-C, Cut&Run, CRISPR-Cas9 survival dropout screening, time-solved deep proteomic and phosphoproteomic analyses in cells carrying auxin-induced degron at endogenous CTCF locus. Acute CTCF protein degradation markedly rewired genome-wide chromatin accessibility. Increased accessible chromatin regions were largely located adjacent to CTCF-binding sites at promoter regions and insulator sites and were associated with enhanced transcription of nearby genes. In addition, we used CTCF-associated multi-omics data to establish a combinatorial data analysis pipeline to discover CTCF co-regulatory partners in regulating downstream gene expression. We successfully identified 40 candidates, including multiple established partners (i.e., MYC) supported by all layers of evidence. Interestingly, many CTCF co-regulators (e.g., YY1, ZBTB7A) that have evident alterations of respective downstream gene expression do not show changes at their expression levels across the multi-omics measurements upon acute CTCF loss, highlighting the strength of our system to discover hidden co-regulatory partners associated with CTCF-mediated transcription. This study highlights CTCF loss rewires genome-wide chromatin accessibility, which plays a critical role in transcriptional regulation
2021-07-04 | PXD026484 | Pride