Nuclear microbiology--bacterial assault on the nucleolus.

Intracellular bacterial pathogens exploit the compartmentalization of the eukaryotic cell to create an environment that supports their own survival and growth. Among cellular organelles, the nucleus has long been considered to be mostly ‘safe’ from direct bacterial attacks. However, a growing number of molecules secreted by bacteria—termed ‘nucleomodulins’—target this central organelle to subvert the host defences of plants and animals [1]. The nucleus itself is a spatially organized compartment, with distinct chromosome territories and many non-membranedelineated nuclear bodies. The most prominent of such subnuclear structures is the nucleolus, which is the site of both ribosomal RNA (rRNA) synthesis and the assembly of ribosomal subunits. In this issue of EMBO reports, new research by Ting Li, Feng Shao and colleagues shows that bacterial pathogens, such as Legionella and Burkholderia spp., can hijack the nucleolus by secreting SET-domain effectors that target and modify rDNA chromatin (Fig 1; [2]). This activates rDNA transcription and promotes bacterial intracellular survival. SET-related proteins exist in diverse bacterial species, which suggests that controlling rDNA transcription in the nucleolus might be a general virulence strategy. In eukaryotic cells, the state of chromatin compaction has a major role in nuclear processes requiring access to DNA. Compaction is regulated by a plethora of histone posttranslational modifications (PTMs), and catalysed by a wide range of enzymes termed ‘writers’, such as histone methyltransferases (HMTases). Histone marks created by these enzymes can either activate (for example, H3K4me) or repress (for example, H3K9me and H3K27me) transcription. Histone PTMs serve as signalling platforms that recruit regulatory proteins, termed ‘readers’, which themselves recruit or stabilize other chromatin components. Readers are docked to histone PTMs through chromatinbinding modules. One such reader is heterochromatin protein 1 (HP1), which binds to H3K9me2/3 by its chromodomain and contributes mainly to heterochromatin formation and gene silencing. Bacterial pathogens can alter host chromatin structure, and thus gene expression, by interfering with signalling pathways that regulate histone-modifying enzymes or by producing mimics of these enzymes [3]. The first example of a bacterial HMTase mimic was discovered in the human pathogen Chlamydia trachomatis by finding a secreted protein, nuclear effector (NUE), that has sequence similarities with eukaryotic SET-domain-containing lysine-specific methyltransferases. NUE enters the nucleus and associates with chromatin (Fig 1; [4]). However, although NUE methylates mammalian histones in vitro, its target genes in the host infected cell remain unknown. Li and colleagues have now identified a SET-domain-containing protein in the opportunistic bacterial pathogen Legionella Nuclear microbiology—bacterial assault on the nucleolus