AI Article Synopsis
- The study investigates the role of CTCF, in collaboration with cohesin, in shaping chromatin structure and gene regulation during the differentiation of mouse embryonic stem cells into neural precursor cells.
- Researchers found that CTCF binding at promoters is crucial for maintaining enhancer-promoter interactions, which significantly impact gene expression, particularly for genes reliant on long-distance enhancers.
- The loss of CTCF binding led to reduced transcription and enhancer-promoter contacts, but restoring CTCF at promoters reinstated these interactions, highlighting its essential role in regulating over 2,000 genes across different adult tissues.
Article Abstract
The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913465 | PMC |
| http://dx.doi.org/10.1038/s41594-020-00539-5 | DOI Listing |
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