Estrogen-induced chromatin looping changes identify a subset of functional regulatory elements
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ABSTRACT:
PROVIDER: PRJNA1123204 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29381344_1.fastq.gz | Fastqsanger.gz | |||
| SRR29381344_2.fastq.gz | Fastqsanger.gz | |||
| SRR29381345_1.fastq.gz | Fastqsanger.gz | |||
| SRR29381345_2.fastq.gz | Fastqsanger.gz | |||
| SRR29381346_1.fastq.gz | Fastqsanger.gz |
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Project description:Estrogen signaling in breast cancer cells relies on long-range chromatin interactions connecting distal regulatory elements bound by the estrogen receptor 1 (ESR1) to target gene promoters. This ensures stimulus and subtype-specific transcriptional responses. Expanding on the function of CTCF and the cohesin complex in breast cancer, we demonstrate that the chromatin-looping factor ZNF143 binds the promoter of most early-response estrogen target genes connected to distal regulatory elements in ESR1-positive breast cancer cells. Its chromatin occupancy is unaffected by estrogen stimulation, supporting a stable three-dimensional genomic architecture within the early response to estrogen. Its loss abrogates the estrogen-induced transcriptional response and growth of breast cancer cells. When taking into account CTCF, ZNF143 and cohesin complex subunits, we show that chromatin-looping factors are genetically altered in over 20% of ESR1-positive primary breast tumors. Furthermore, the overexpression of ZNF143, CTCF and RAD21, a cohesin complex subunit, in ESR1-positive breast tumors associates with a worse clinical outcome. Overall, our results suggest that ZNF143 is a new critical effector of the estrogen response and highlights the contribution of the chromatin looping machinery to ESR1-positive breast cancer development. mRNA profiles of MCF-7 cells (siCtl or siZNF143) under vehicle (EtOH) or E2 (10 uM 17-beta oestradiol) stimulation
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