Abstract
In Schizosaccharomyces pombe, transcripts derived from the pericentromeric dg and dh repeats promote heterochromatin formation via RNAi as well as an RNAi-independent mechanism involving the RNA polymerase II (RNAPII)-associated RNA-binding protein Seb1 and RNA processing activities. We show that Seb1 promotes long-lived RNAPII pauses at pericentromeric repeat regions and that their presence correlates with the heterochromatin-triggering activities of the corresponding dg and dh DNA fragments. Globally increasing RNAPII stalling by other means induces the formation of novel large ectopic heterochromatin domains. Such ectopic heterochromatin occurs even in cells lacking RNAi. These results uncover Seb1-mediated polymerase stalling as a signal necessary for heterochromatin nucleation.
Highlights
Packaging of pericentromeric DNA into heterochromatin is crucial for genome stability, development, and health, yet its endogenous triggers remain poorly understood (Allshire and Madhani 2018)
We show that Seb1, whose role in heterochromatin we established in prior work (Marina et al 2013), displays extensive binding to dg and dh repeat RNAs and promotes long-lived pausing by RNA polymerase II (RNAPII)
These data indicate that the seb1-1 allele leads to decreased RNAPII pausing at gene 5′ ends with an associated increased 3′ signal; the latter may be due to polymerase release from upstream pauses
Summary
Packaging of pericentromeric DNA into heterochromatin is crucial for genome stability, development, and health, yet its endogenous triggers remain poorly understood (Allshire and Madhani 2018). Dhp, and SHREC promote RNAi-independent pericentromeric heterochromatin assembly at pericentromeric regions (Marina et al 2013; Chalamcharla et al 2015; Tucker et al 2016), while Rrp and Mlo inhibit it (Reyes-Turcu et al 2011) Other fungi, such as Neurospora crassa and Cryptococcus neoformans, as well as somatic mammalian cells do not require RNAi for heterochromatin assembly (Freitag et al 2004; Wang et al 2010; Chan and Wong 2012); poorly understood RNAi-independent mechanisms are important to investigate. The cleavage polyadenylation (CPA) machinery antagonizes silencing, suggesting a possible mechanism by which heterochromatin is limited at mRNA-coding genes despite the presence of termination-associated pauses These findings establish a role for Seb1-dependent RNAPII pausing in promoting the formation of repressive chromatin structures
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