Global regulation of heterochromatin spreading by Leo1.

Laure Verrier,Ramon R Barrales,Sigurd Braun,Francesca Taglini,Takeshi Urano,Elizabeth H Bayne,Shaun Webb

doi:10.1098/rsob.150045

Abstract

Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined boundaries and thus prevent silencing of expressed genes. Here we show that loss of the PAF complex (PAFc) component Leo1 compromises chromatin boundaries, resulting in invasion of heterochromatin into flanking euchromatin domains. Similar effects are seen upon deletion of other PAFc components, but not other factors with related functions in transcription-associated chromatin modification, indicating a specific role for PAFc in heterochromatin regulation. Loss of Leo1 results in reduced levels of H4K16 acetylation at boundary regions, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1Δ cells, suggesting that Leo1 antagonises heterochromatin spreading by promoting H4K16 acetylation. Our findings reveal a previously undescribed role for PAFc in regulating global heterochromatin distribution.

Highlights

The organization of eukaryotic genomes is fundamental to their integrity and regulation
We found that deletion of the PAF complex (PAFc) component Leo1 causes centromeric heterochromatin to spread across normal boundaries and invade euchromatin
(electronic supplementary material, figure S1), we identified leo1þ as a novel gene required to prevent silencing of IRC1L:ura4þ locus (IRC1L):ura4þ

Summary

Introduction

The organization of eukaryotic genomes is fundamental to their integrity and regulation. Repressive chromatin, called heterochromatin, is characterized by low levels of histone acetylation and high levels of methylation at lysine 9 of histone H3 (H3K9me2) [2]. It has a compacted structure largely refractory to transcription, and is typically associated with transcriptional repression of underlying genes. While gene-rich regions are usually euchromatic, domains of heterochromatin such as those found at centromeres and telomeres play important roles in genome stability, contributing to centromere function, repression of recombination and maintenance of telomere integrity [2]

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Discussion

Conclusion