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ChipSeq of Twist1 and YY1 in PLC-PRF-5 cells

ABSTRACT: Epithelial–mesenchymal transition (EMT) is an important mechanism of metastasis and malignant progression of hepatocellular carcinoma (HCC). However, the transcriptional regulation mechanism of EMT remains poorly understood. Some transcriptional co-activators can form phase-separated condensates at super-enhancers that compartmentalize and concentrate the transcription apparatus to drive robust gene expression. Here, we demonstrate that Twist1 and YY1, interact with p300 and form phase-separated local high-concentration interaction hubs at super-enhancers of miRNA-9 and activate its expression to induce EMT and promote the malignant evolution of HCC. Phase separation disrupted by metformin perturbs Twist–YY1 condensates, thereby inhibiting EMT. To explore how the Twist1 complex regulates miR-9 expression by binding SE region, we performed Twist1 ChIP-seq combined with H3K4me3, H3K4me1, H3K27ac, DNAse, p300, and YY1 ChIP-seq data to detect the SEs of miR-9. After metformin treatment, the peak of Twist1/YY1 on miR-9 SE decreased. Metformin specifically affects the binding of Twist1/YY1 to the miR-9 SE region. 1,6-hexanediol, as an aliphatic alcohol, can weaken hydrophobic interactions and inhibit liquid–liquid phase separation by disrupting hydrophobic interactions. In order to prove Twist1/YY1 interaction at these sites requires phase separation, we detect the accessibility of miR-9 SE regions in 1,6-hexanediol-treated cells. The result showed a general decrease in the accessibility of miR-9 super-enhancer regions in 1,6-hexanediol-treated cells and Twist1 / YY1 combines the SE region of miR-9 in the form of phase separation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141965 | GEO | 2019/12/13

REPOSITORIES: GEO

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ATAC-seq profiling of open chromatin in PLC-PRF cells

Project description:Epithelial–mesenchymal transition (EMT) is an important mechanism of metastasis and malignant progression of hepatocellular carcinoma (HCC). However, the transcriptional regulation mechanism of EMT remains poorly understood. Some transcriptional co-activators can form phase-separated condensates at super-enhancers that compartmentalize and concentrate the transcription apparatus to drive robust gene expression. Here, we demonstrate that Twist1 and YY1, interact with p300 and form phase-separated local high-concentration interaction hubs at super-enhancers of miRNA-9 and activate its expression to induce EMT and promote the malignant evolution of HCC. Phase separation disrupted by metformin perturbs Twist–YY1 condensates, thereby inhibiting EMT. To explore how the Twist1 complex regulates miR-9 expression by binding SE region, we performed Twist1 ChIP-seq combined with H3K4me3, H3K4me1, H3K27ac, DNAse, p300, and YY1 ChIP-seq data to detect the SEs of miR-9. After metformin treatment, the peak of Twist1/YY1 on miR-9 SE decreased. Metformin specifically affects the binding of Twist1/YY1 to the miR-9 SE region. 1,6-hexanediol, as an aliphatic alcohol, can weaken hydrophobic interactions and inhibit liquid–liquid phase separation by disrupting hydrophobic interactions. In order to prove Twist1/YY1 interaction at these sites requires phase separation, we detect the accessibility of miR-9 SE regions in 1,6-hexanediol-treated cells. The result showed a general decrease in the accessibility of miR-9 super-enhancer regions in 1,6-hexanediol-treated cells and Twist1 / YY1 combines the SE region of miR-9 in the form of phase separation.

2019-12-13 | GSE141964 | GEO

Coactivator condensation at super-enhancers links phase separation and gene control (RNA-Seq)

Project description:Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. We recently proposed that a phase-separated multi-molecular assembly underlies the formation and function of SEs. Here, we demonstrate that the SE-enriched factors BRD4 and MED1 form nuclear puncta that occur at SEs and exhibit properties of liquid-like condensates. Disruption of BRD4 and MED1 puncta by 1,6-hexanediol is accompanied by a loss of BRD4 and MED1 at SEs and a loss of RNAPII from SE-driven genes. We find that the intrinsically disordered regions (IDRs) of BRD4 and MED1 are sufficient to form phase-separated droplets in vitro and the MED1 IDR promotes phase separation in living cells. The MED1 IDR droplets are capable of compartmentalizing BRD4 and other transcriptional machinery in nuclear extracts. These results support the idea that SEs form phase-separated condensates that compartmentalize the transcription apparatus at key genes, provide insights into the role of cofactor IDRs in this process, and offer new insights into mechanisms involved in control of key cell identity genes.

2018-04-07 | GSE112807 | GEO

Coactivator condensation at super-enhancers links phase separation and gene control (ChIP-Seq)

2018-04-07 | GSE112806 | GEO

Suppression of liquid-liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

Project description:Liquid-liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within the cell nucleus. However, the role played by LLPS in chromatin folding in living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) and Hi-C techniques, we studied the effects of 1,6-hexanediol (1,6-HD)- mediated LLPS disruption/modulation on higher-order chromatin organization in living cells. We found that 1,6-HD treatment caused the enlargement of nucleosome clutches and their more uniform distribution in the nuclear space. At a megabase-scale, chromatin underwent moderate but irreversible perturbations that resulted in the partial mixing of A and B compartments. The removal of 1,6-HD from the culture medium did not allow chromatin to acquire initial configurations, and resulted in more compact repressed chromatin than in untreated cells. 1,6-HD treatment also weakened enhancer-promoter interactions and TAD insulation but did not considerably affect CTCF-dependent loops. Our results suggest that 1,6-HD-sensitive LLPS plays a limited role in chromatin spatial organization by constraining its folding patterns and facilitating compartmentalization at different levels.

2021-03-22 | GSE138543 | GEO

Suppression of liquid-liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

Project description:Suppression of liquid-liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells

| PRJNA576273 | ENA

K562 cell lime LC-MSMS,Quantitative measurement of hydrophobicity dependent LLPS property of chromatin condensate

Project description:K562 cell line treated with 1,6-HD and proteins were captured via cross-linking. We quantified chromatin structure changes and chromatin binding proteins in K562 cell before and after 1,6-hexanediol treatment by Hi-C and Hi-MS, respectively.

2021-07-26 | PXD021434 | Pride

Peptidyl-prolyl isomerase Cyclophilin 71 promotes SERRATE phase separation and miRNA processing in Arabidopsis [mRNA-Seq]

Project description:MicroRNAs (miRNAs) play an important role in gene regulation. In Arabidopsis thaliana, mature miRNAs are processed from primary miRNA transcripts by Dicing complex, which contains DCL1, SE and HYL1 and forms nuclear dicing bodies (D-bodies) through SE phase separation. Here we report that Cyclophilin 71 (CYP71), a peptidyl-prolyl isomerase (PPIase), positively regulates miRNA processing. We show that CYP71 directly interacts with SE and enhances its phase separation, thereby promoting the formation of D-body and increasing the activity of Dicing complex. We further show that the PPIase activity is important for the function of CYP71 in miRNA production. Our findings reveal orchestration of miRNA processing by a cyclophilin protein and suggest the involvement of proline cis-trans isomerization, a structural mechanism, in SE phase separation and miRNA processing.

2023-08-07 | GSE235656 | GEO

Peptidyl-prolyl isomerase Cyclophilin 71 promotes SERRATE phase separation and miRNA processing in Arabidopsis [miRNA-Seq]

2023-08-07 | GSE207396 | GEO

Chip-seq of H3K4me3, H3K4me1, H3K27ac and P300 in HCC cells

Project description:Considered as fundamental epigenetic regulators controlling many key cellular processes, histone modifications are a well-conserved and widely studied class of epigenetic modifications. Genome-wide studies have identified enhancers as DNA sequences that bind to H3K4me1 and H3K27ac and promoters as DNA sequences that bind to H3K4me3. To explore how the Twist1 complex (Twist1/YY1/p300) regulates miR-9 expression, we performed ChIP-seq in PLC-PRF-5 cells, providing a panorama of p300, H3K4me3, H3K4me1, and H3K27ac.

2022-07-21 | GSE208334 | GEO

TWIST1-induced microRNA-424 drives an intermediate epithelial-to-mesenchymal transition that opposes metastasis

Project description:Epithelial-to-mesenchymal transition (EMT) is a dynamic process that relies on cellular plasticity; an EMT/MET axis is critical for metastatic colonization of carcinomas. Unlike epithelial programming, regulation of mesenchymal programming is not well understood in EMT. Here we describe the first microRNA that enhances exclusively mesenchymal programming. We demonstrate that microRNA-424 is up-regulated early during a TWIST1/SNAI1-induced EMT, and that it causes cells to express mesenchymal genes without affecting epithelial genes, resulting in a mixed/intermediate EMT. Further, microRNA-424 increases motility, decreases adhesion and induces a growth arrest, changes associated with a complete EMT. Patient microRNA-424 levels positively associate with TWIST1/2 and EMT-like gene signatures and is increased in primary tumors versus matched normal breast. However, microRNA-424 is down-regulated in metastases versus matched primary tumors. Correspondingly, microRNA-424 decreases tumor initiation and is post-transcriptionally down-regulated in macrometastases in mice. RNA-seq identified microRNA-424 regulates numerous genes associated with EMT and breast cancer stemness including the novel miR-424 target, TGFBR3, which regulates mesenchymal phenotypes without influencing miR-424 effects on tumor-initiating phenotypes; instead, we show that ERK signaling is critical for such tumor-initiating effects of miR-424. These findings suggest microRNA-424 plays distinct roles downstream of EMT-inducing factors, facilitating earlier stages, but repressing later stages, of metastasis. Examination of mRNA levels in MCF12A human breast cell lines that stably over-expressed miR-424 or an empty vector (EV) control. Each group has three replicates.

2015-02-26 | E-GEOD-54505 | biostudies-arrayexpress

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