RNA polymerase backtracking results in the accumulation of fission yeast condensin at active genes

Abstract

The mechanisms leading to the accumulation of the SMC complexes condensins around specific transcription units remain unclear. Observations made in bacteria suggested that RNA polymerases (RNAPs) constitute an obstacle to SMC translocation, particularly when RNAP and SMC travel in opposite directions. Here we show in fission yeast that gene termini harbour intrinsic condensin-accumulating features whatever the orientation of transcription, which we attribute to the frequent backtracking of RNAP at gene ends. Consistent with this, to relocate backtracked RNAP2 from gene termini to gene bodies was sufficient to cancel the accumulation of condensin at gene ends and to redistribute it evenly within transcription units, indicating that RNAP backtracking may play a key role in positioning condensin. Formalization of this hypothesis in a mathematical model suggests that the inclusion of a sub-population of RNAP with longer dwell-times is essential to fully recapitulate the distribution profiles of condensin around active genes. Taken together, our data strengthen the idea that dense arrays of proteins tightly bound to DNA alter the distribution of condensin on chromosomes.

Context-dependent transcriptional remodeling of TADs during differentiation

“…Release of this pause on full transcription in DP cells re-widens the TAD boundary again, which could be explained if the polymerase acted as a mobile loop extrusion barrier. Similar gene body-broadened boundaries have recently been reported on metagene analysis in a parallel study (Banigan et al, 2022), and we have recently proposed in fission yeast that paused or backtracking RNA polymerase may have different effects on condensin-mediated loop extrusion to elongating polymerase (Rivosecchi et al, 2021). Ectopic induction of the gene had no effect on local chromatin topology in ESCs, but the boundary was already rather wide, so the model is not necessarily disproved.…”

RNA surveillance controls 3D genome structure via stable cohesin-chromosome interaction

“…We considered that RNAPII accumulated in the intergenic region of the convergent genes could be a trace of RNAPII backtracking activity and a recent study also reported that backtracking of RNA polymerase induces the accumulation of condensin (Rivosecchi et al, 2021). Consistent with a previous study in mammalian cells (Busslinger et al, 2017), at symmetrically expressed sites, Rad21 was positioned symmetrically, and this correlated with the accumulated Ser2P signals at the same converging intergenic sites.…”

“…Recently, a study in fission yeast reported that the RNA polymerase backtracking at gene termini might contribute to the accumulation of condensin, another SMC complex (Rivosecchi et al, 2021).…”

Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase

“…Given the presence of condensin-dependent TADs at subtelomeres, it is tempting to speculate that condensin-mediated loop extrusion ( 2, 3 ) provides the power stroke to disentangle telomeres, even when Top2 is impaired thanks to the proximity of DNA ends. By analogy with the enrichment of condensin at highly expressed genes ( 22, 23 ), Taz1 bound to telomeres might create an obstacle onto which loop-extruding condensin complexes accumulate in metaphase (Fig. 4D).…”