FACT Facilitates Transcription-Dependent Nucleosome Alteration

TLDR

The FACT complex is essential for RNA polymerase II to elongate transcripts through nucleosomes in vitro. FACT promotes Pol II transcription through chromatin by destabilizing nucleosomes, removing an H2A–H2B dimer, and acting as a histone chaperone that deposits core histones, a process that depends on both subunits and the acidic C‑terminus of Spt16 and preserves epigenetic integrity.

Abstract

The FACT (facilitates chromatin transcription) complex is required for transcript elongation through nucleosomes by RNA polymerase II (Pol II) in vitro. Here, we show that FACT facilitates Pol II-driven transcription by destabilizing nucleosomal structure so that one histone H2A-H2B dimer is removed during enzyme passage. We also demonstrate that FACT possesses intrinsic histone chaperone activity and can deposit core histones onto DNA. Importantly, FACT activity requires both of its constituent subunits and is dependent on the highly acidic C terminus of its larger subunit, Spt16. These findings define the mechanism by which Pol II can transcribe through chromatin without disrupting its epigenetic status.