CTCF is a critical protein known to play various roles in key biological processes such as transcription. Scientists at St. Jude Children's Research Hospital have used a next-generation protein degradation technology to study CTCF. Their work revealed the superiority of the approach in addition to providing functional insights into how CTCF regulates transcription. The study, published today in Genome Biology, paves the way for more clear, nuanced studies of CTCF.
. In the protein's absence, researchers can study the functional changes that occur, providing insight into how the protein influences a cell. One system for degrading proteins is the auxin-inducible degron 1 system. However, this system places limitations on accurate investigation of the function of CTCF, such as the high dosage dependency of auxin, which causes cellular toxicity that muddles results.
"We've cracked open the understanding of the impact of CTCF using a degradation model, the AID2 system," said co-corresponding author Chunliang Li, Ph.D., St. Jude Department of Tumor Cell Biology."Using this system, we identified the rules that govern CTCF-dependent transcription regulation." "With degradation we can create a very clean background, and then introduce a mutant. This switch happens very fast, so we call it a fast-swapping system," Li said."This is the first time a clean and fast-swapping system has been used to study individual mutants of CTCF."
"CTCF itself is a multifunctional protein," said co-first author Judith Hyle, St. Jude Department of Tumor Cell Biology."It has various roles in a cell from chromatin architecture maintenance to transcription regulation, either as an activator or repressor of transcription. Our interest is how CTCF is involved in transcriptional regulation, and with this new system we were able to degrade CTCF much more rapidly, and home in on the specific targets of CTCF.
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