Polymerase pausing induced by sequence-specific RNA-binding protein drives heterochromatin assembly
| Autor: | Selim Boudoukha, Jordan E. Burke, Christina M. Homer, Hiten D. Madhani, Jahan-Yar Parsa |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Euchromatin Heterochromatin RNA polymerase II RNA-binding protein 03 medical and health sciences chemistry.chemical_compound RNA interference Schizosaccharomyces Centromere Genetics Heterochromatin assembly Polymerase biology Methyltransferase complex EZH2 fungi Nuclear Proteins RNA-Binding Proteins Chromatin Assembly and Disassembly Cell biology 030104 developmental biology chemistry biology.protein RNA Interference Heterochromatin protein 1 RNA Polymerase II Schizosaccharomyces pombe Proteins DNA Research Paper Microsatellite Repeats Developmental Biology |
| Zdroj: | Genes & Development. 32:953-964 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.310136.117 |
| Popis: | Packaging of pericentromeric DNA into heterochromatin is crucial for genome stability, development and health, yet its endogenous triggers remain poorly understood1. A defining feature of pericentromeric heterochromatin is histone H3 lysine 9 methylation (H3K9me)2–4. In S. pombe, transcripts derived from the pericentromeric dg and dh repeat during S phase5–7 promote heterochromatin formation through two pathways: an RNAi-dependent mechanism involving recruitment of the Clr4 H3K9 methyltransferase complex (CLR-C) via the RITS complex8–13, and RNAi-independent mechanism involving an RNAPII-associated RNA-binding protein Seb1, the repressor complex SHREC, and RNA processing activities14–19. We show here that Seb1 promotes long-lived RNAPII pausing. Pause sites associated with sequence-specific Seb1 RNA binding events are significantly enriched in pericentromeric repeat regions and their presence correlates with the heterochromatin-triggering activities of the corresponding dg and dh DNA fragments. Remarkably, globally increasing RNAPII stalling by other means induces the formation of novel large ectopic heterochromatin domains. Such ectopic heterochromatin occurs even in cells lacking functional RITS, demonstrating that RNAPII pausing can be sufficient to trigger de novo heterochromatin independently of RNAi. These results uncover Seb1-mediated polymerase stalling as a new signal for nucleating heterochromatin assembly in repetitive DNA. |
| Databáze: | OpenAIRE |
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