Chromatin remodeller Fun30Fft3 induces nucleosome disassembly to facilitate RNA polymerase II elongation

Abstract

Previous studies have revealed that nucleosomes impede elongation of RNA polymerase II (RNAPII). Recent observations suggest a role for ATP-dependent chromatin remodellers in modulating this process, but direct in vivo evidence for this is unknown. Here using fission yeast, we identify Fun30Fft3 as a chromatin remodeller, which localizes at transcribing regions to promote RNAPII transcription. Fun30Fft3 associates with RNAPII and collaborates with the histone chaperone, FACT, which facilitates RNAPII elongation through chromatin, to induce nucleosome disassembly at transcribing regions during RNAPII transcription. Mutants, resulting in reduced nucleosome-barrier, such as deletion mutants of histones H3/H4 themselves and the genes encoding components of histone deacetylase Clr6 complex II suppress the defects in growth and RNAPII occupancy of cells lacking Fun30Fft3. These data suggest that RNAPII utilizes the chromatin remodeller, Fun30Fft3, to overcome the nucleosome barrier to transcription elongation.

The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes

“…Depletion of this enzyme results in an open chromatin conformation in normally transcriptionally repressed regions and can affect gene expression, suggesting that SMARCAD1 ensures correct chromatin structure of silent domains. SMARCAD1 can also activate transcription together with co-activator p300/CBP (CREB-binding protein), and interactions with the transcription machinery have recently been reported in S. pombe (20,21). In addition, SMARCAD1 is involved in double-strand break repair (22).…”

A role for histone acetylation in regulating transcription elongation

“…Indeed, Swi-Snf has been shown to cooperate with, or work in parallel to, Asf1 to displace nucleosomes at the HO promoter and PHO5 / PHO8 promoters, respectively [35,36]. More recent work in fission yeast has also provided direct in vivo evidence to show that the Fun30 Fft3 ATP-dependent chromatin remodelling complex cooperates with the FACT histone chaperone to promote nucleosome eviction within ORFs to enable Pol II elongation [37]. Thus, we hypothesise that the concerted action of histone H3K14ac, ATP-dependent chromatin remodelling complexes and histone chaperones would be required to promote histone eviction at the ORF to allow Pol II elongation (Figure 2).…”

Evidence that dissociation of Spt16 from transcribed genes is partially dependent on RNA Polymerase II termination

“…The model for FACT-nucleosome interactions derived from in vitro studies is likely descriptive of FACT's action on nucleosomes during transcription in vivo, but does not provide immediate insight into the mechanisms that govern FACT recruitment to genes nor its dissociation from genes once the transcription process is complete. Experiments carried out in various model systems have provided evidence that a number of protein factors and histone modifications are directly or indirectly involved in FACT recruitment to transcribed genesthese include Pol II itself, the chromatin remodelers Chd1 and Fun30, the mRNA capping enzyme Cet1, heterochromatin protein 1 (HP1), the protein complexes Paf1C and NuA3, acetylated histone H3 tails, and the histone modifications H3-K36me3, H3-K4me3 and H2B-K123Ub ( [29][30][31][32] and reviewed in [11]). The nucleosome acidic patch has also been shown to play roles in promoting FACT association with genes [33][34][35] and other recent studies have provided compelling evidence that nucleosomes that have been disrupted through interactions with transcribing Pol II can also promote FACT localization over transcribed genes [36].…”