The research paper from the Fukaya Lab has been published in the Science Advances!

Decoding the molecular logic of rapidly evolving ZAD zinc finger proteins in Drosophila

Raku Saito, Yusuke Umemura, Shiho Makino, Takashi Fukaya

Abstract
The zinc finger–associated domain (ZAD)–containing C2H2 zinc finger proteins (ZAD-ZnFs) represent the most abundant class of transcription factors that emerged during insect evolution, yet their molecular diversity and biological functions remain largely unclear. Here, we established a systematic CRISPR-based protein-tagging approach that enables direct, unambiguous comparison of nuclear localization and genome-wide binding profiles of endogenous ZAD-ZnFs in developing Drosophila embryos. Evidence is provided that a subset of ZAD-ZnFs forms nuclear condensates through the stacking of the N-terminal ZAD dimerization surface. Disruption of condensation activity leads to misregulation of genome-wide binding profiles and lethality, underscoring its functional and physiological significance in development. Integrative chromatin immunoprecipitation sequencing and Micro-C analyses reveal that many ZAD-ZnFs colocalize with core insulator proteins such as CCCTC-binding factor and Centrosomal protein 190 kD to control the formation of topological boundaries. We suggest that the diverse molecular functions of ZAD-ZnFs have evolutionarily arisen from their ancestral role as insulator-binding proteins.

Science Advances, doi: 10.1126/sciadv.ady7568. (2026)
https://www.science.org/doi/10.1126/sciadv.ady7568