Xinyu Feng

All Publications

• GAGA zinc finger transcription factor searches chromatin by 1D-3D facilitated diffusion. Nature structural & molecular biology Feng, X. A., Yamadi, M., Fu, Y., Ness, K. M., Liu, C., Ahmed, I., Bowman, G. D., Johnson, M. E., Ha, T., Wu, C. 2025

  Abstract

  The search for target sites on chromatin by eukaryotic sequence-specific transcription factors (TFs) is integral to the regulation of gene expression but the mechanism of nuclear exploration has remained obscure. Here we use multicolor single-molecule fluorescence resonance energy transfer and single-particle imaging to track the diffusion of purified Drosophila GAGA factor (GAF) on DNA and nucleosomes. Monomeric GAF DNA-binding domain (DBD) bearing one zinc finger finds its cognate site through one-dimensional (1D) or three-dimensional (3D) diffusion on bare DNA and rapidly slides back and forth between naturally clustered motifs for seconds before dissociation. Multimeric, full-length GAF also finds clustered motifs on DNA through 1D-3D diffusion but remains locked on target for longer periods. Nucleosome architecture effectively blocks GAF-DBD 1D sliding into the histone core but favors retention of GAF-DBD once it has bound to a solvent-exposed motif through 3D diffusion. Despite the occlusive nature of nucleosomes, 1D-3D facilitated diffusion enables GAF to effectively search for clustered cognate motifs in chromatin, providing a mechanism for navigation to nucleosomal and nucleosome-free sites by a member of the zinc finger TF family.

  View details for DOI 10.1038/s41594-025-01643-0

  View details for PubMedID 40764461

• Dynamic 1D search and processive nucleosome translocations by RSC and ISW2 chromatin remodelers ELIFE Kim, J., Carcamo, C. C., Jazani, S., Xie, Z., Feng, X. A., Yamadi, M., Poyton, M., Holland, K. L., Grimm, J. B., Lavis, L. D., Ha, T., Wu, C. 2024; 12

  Abstract

  Eukaryotic gene expression is linked to chromatin structure and nucleosome positioning by ATP-dependent chromatin remodelers that establish and maintain nucleosome-depleted regions (NDRs) near transcription start sites. Conserved yeast RSC and ISW2 remodelers exert antagonistic effects on nucleosomes flanking NDRs, but the temporal dynamics of remodeler search, engagement, and directional nucleosome mobilization for promoter accessibility are unknown. Using optical tweezers and two-color single-particle imaging, we investigated the Brownian diffusion of RSC and ISW2 on free DNA and sparse nucleosome arrays. RSC and ISW2 rapidly scan DNA by one-dimensional hopping and sliding, respectively, with dynamic collisions between remodelers followed by recoil or apparent co-diffusion. Static nucleosomes block remodeler diffusion resulting in remodeler recoil or sequestration. Remarkably, both RSC and ISW2 use ATP hydrolysis to translocate mono-nucleosomes processively at ~30 bp/s on extended linear DNA under tension. Processivity and opposing push-pull directionalities of nucleosome translocation shown by RSC and ISW2 shape the distinctive landscape of promoter chromatin.

  View details for DOI 10.7554/eLife.91433

  View details for Web of Science ID 001187171500001

  View details for PubMedID 38497611

  View details for PubMedCentralID PMC10948146