Roles of the Histone Chaperone FACT in Drosophila Gene Regulation and Chromatin Architecture

• DOI: 10.1096/fasebj.30.1_supplement.lb108
• Publication Date: 2023-11-26T16:23:51Z
• Authors: Theophilus Tettey; Benjamin Story; Robert L Glaser; Marco Blanchette; Joan W Conaway; Ronald C Conaway

The highly conserved histone chaperone FACT (Facilitates Chromatin Transcription) is thought to contribute to the disassembly and reassembly of nucleosomes in the wake of RNA polymerase II passage through chromatin. In yeast, mutation of FACT subunits leads to decreased nucleosome occupancy at the promoters and transcribed regions of genes. In addition, genetic experiments suggest that yeast FACT plays a critical role in restricting initiation of transcription to normal promoters, ensuring that only appropriate mRNAs are synthesized. However, FACT's roles in chromatin biology and transcriptional regulation in higher eukaryotes are not well understood. Using Drosophila S2 cells as a model, we observe that depletion of the FACT complex results in aberrant transcriptional regulation. Surprisingly, we observe in genome‐wide experiments that FACT depletion has little effect on total nucleosome occupancy or position, but dramatically alters the distribution of various histone modifications, including histone 3 lysine 4 trimethylation (H3K4me3), histone 2A variant (H2Av) and histone 3 lysine 36 trimethylation (H3K36me3), in the promoters and transcribed regions of genes. Our results thus far provide valuable insight into roles of FACT in transcriptional regulation and chromatin dynamics in higher eukaryotes.Support or Funding InformationStowers Institute for Medical Research