A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing

Abstract

Summary: FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as an activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis of FACT function in Pol II transcription in Drosophila. We present evidence that loss of FACT has a dramatic impact on Pol II elongation-coupled processes including histone H3 lysine 4 (H3K4) and H3K36 methylation, consistent with a role for FACT in coordinating histone modification and chromatin architecture during Pol II transcription. Importantly, we identify a role for FACT in the maintenance of promoter-proximal Pol II pausing, a key step in transcription activation in higher eukaryotes. These findings bring to light a broader role for FACT in the regulation of Pol II transcription. : FACT is a histone chaperone implicated in the assembly and disassembly of nucleosomes during transcription. Tettey et al. demonstrate that Drosophila FACT regulates patterns of the transcription-coupled histone marks H3K4me3 and H3K36me3 and helps to maintain promoter-proximal Pol II pausing. Keywords: FACT, Spt16, SSRP1, RNA polymerase II, promoter-proximal pausing, chromatin, H3K4me3, H3K36me3, H2A.v, RNA-seq, ChIP-seq, PRO-seq, ChIP-nexus