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Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers [Hi-C]

ABSTRACT: Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers [Hi-C]

PROVIDER: PRJNA703392 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13755461_1.fastq.gz	Fastqsanger.gz
	SRR13755461_2.fastq.gz	Fastqsanger.gz
	SRR13755462_1.fastq.gz	Fastqsanger.gz
	SRR13755462_2.fastq.gz	Fastqsanger.gz
	SRR13755463_1.fastq.gz	Fastqsanger.gz

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Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers [Hi-C]

Project description:Triple-negative breast cancer (TNBC) is malignant cancer with a high risk of recurrence. To date, the underlying 3D chromatin organizations of TNBC have remained unclear. Here, using in situ Hi-C, we characterized the 3D chromatin organizations in cells representing five distinct subtypes of breast cancer (including TNBC) and TNBC tissues, compared to normal cells/tissues. We found that the global and local 3D architectures are severely disrupted in TNBC cells. Importantly, we detected CTCF-dependent TNBC-susceptible loss/gain of 3D chromatin organizations and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulations. Although some discrepancies exist between TNBC cell lines and tissues, we observed that perturbed local 3D architectures found in TNBC cells are partially conserved in TNBC tissues. Furthermore, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. Collectively, our findings provide important features of 3D chromatin organization in TNBC.

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Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers

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Widespread rearrangement of 3D chromatin organization underlies Polycomb-mediated stress-induced silencing [Hi-C]

Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences. Analysis of 3D chromatin organization using Hi-C in Drosophila Kc167 cells. Cells were grown at 25 C and heat shocked for 20 min at 36.5 C. Cells were also treated with flavopiridol or triptolide to inhibit transcription elongation or initiation, respectively. Cells were depeleted of Cap-H2 or Rad21 using RNAi. Finally, cells depleted of RAd21 were subjected to heat shock at 36.5 C for 20 min.

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3D genome organization in the epithelial-mesenchymal transition spectrum [Hi-C]

Project description:3D genome organization in the epithelial-mesenchymal transition spectrum [Hi-C]

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