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Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226217 | GEO | 2023/06/22

REPOSITORIES: GEO

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Cell line-specific features of 3D chromatin organization in hepatocellular carcinoma.

Project description:Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.

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Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [Hi-C]

Project description:Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines—Hep3B, Huh1, Huh7, and SNU449—using in situ Hi-C and ATAC-seq. Our findings revealed that HCCs had elevated long-range interactions compared to HMECs, both intra- and interchromosomal. Unexpectedly, they displayed cell line-specific compartmental modifications at the Mb scale, which could aid in determining HCC subtypes. At the sub-Mb scale, we observed a decrease in intra-TAD interactions and chromatin loops in HCCs compared to HMECs. Lastly, we discovered a correlation between gene expression and 3D chromatin architecture in SLC8A1, which encodes the sodium-calcium antiporter known to induce apoptosis. Our findings suggest that HCCs have a distinct 3D genome organization that is different from normal and other cancer cells. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will lead us to a better understanding of specific gene regulation mechanisms and uncover novel targets for cancer treatments.

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Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [ATAC-seq]

Project description:Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines—Hep3B, Huh1, Huh7, and SNU449—using in situ Hi-C and ATAC-seq. Our findings revealed that HCCs had elevated long-range interactions compared to HMECs, both intra- and interchromosomal. Unexpectedly, they displayed cell line-specific compartmental modifications at the Mb scale, which could aid in determining HCC subtypes. At the sub-Mb scale, we observed a decrease in intra-TAD interactions and chromatin loops in HCCs compared to HMECs. Lastly, we discovered a correlation between gene expression and 3D chromatin architecture in SLC8A1, which encodes the sodium-calcium antiporter known to induce apoptosis. Our findings suggest that HCCs have a distinct 3D genome organization that is different from normal and other cancer cells. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will lead us to a better understanding of specific gene regulation mechanisms and uncover novel targets for cancer treatments.

2023-06-22 | GSE226215 | GEO

Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma

Project description:Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma

| PRJNA939172 | ENA

Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [ATAC-seq]

Project description:Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [ATAC-seq]

| PRJNA939173 | ENA

Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [Hi-C]

Project description:Cell Line-Specific Features of 3D Chromatin Organization in Hepatocellular Carcinoma [Hi-C]

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Widespread rearrangement of 3D chromatin organization underlies Polycomb-mediated stress-induced silencing

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Hepatocellular Carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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ChIPr: accurate prediction of cohesin-mediated 3D genome organization from 2D chromatin features.

Project description:The three-dimensional genome organization influences diverse nuclear processes. Here we present Chromatin Interaction Predictor (ChIPr), a suite of regression models based on deep neural networks, random forest, and gradient boosting to predict cohesin-mediated chromatin interaction strength between any two loci in the genome. The predictions of ChIPr correlate well with ChIA-PET data in four cell lines. The standard ChIPr model requires three experimental inputs: ChIP-Seq signals for RAD21, H3K27ac, and H3K27me3 but works well with just RAD21 signal. Integrative analysis reveals novel insights into the role of CTCF motif, its orientation, and CTCF binding on cohesin-mediated chromatin interactions.

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