Chromatin accessibility: A new avenue for gene editing

In a study recently published in Nature Genetics, researchers from Nano Life Science Institute (WPI-NanoLSI), Kanazawa University explore chromatin accessibility, i.e., endogenous access pathways to the genomic DNA, and its use as a tool for gene editing. Researchers from Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, led by Yusuke Miyanari, have used advanced genetic screening methods to unravel chromatin accessibility and its pathways.

For the investigation, the team used a combination of two technologies CRISPR screening and ATAC-see. While the former is a method to suppress the function of a desired set of genes, the latter is a means to identify which ones are essential for chromatin accessibility. Thus, using this method all genes playing a crucial role in chromatin accessibility could be pinned down.

With the help of these assays, novel pathways and individual players involved in chromatin accessibility were uncovered some playing a positive role and some negative. Of these, one particular protein, TFDP1, showed a negative effect on chromatin accessibility. When it was suppressed, a significant increase in chromatin accessibility was observed, accompanied by nucleosome reduction. A deeper dive into the mechanism of TFDP1 revealed that it functions by regulating the genes responsible for production of certain histone proteins. The team then focused their study toward exploring biotechnological applications of their findings. After suppressing TFDP1, two different approaches were tried. The first approach involved gene editing using the CRISPR/Cas9 tool. This revealed that deletion of TFDP1 made the gene editing process easier.