Type IV secretion systems (T4SS) are multicomponent machineries involved in the translocation of effector molecules across the bacterial cell envelope. The virB operon of Brucella abortus codes for a T4SS that is essential for virulence and intracellular multiplication of the bacterium in the host. Previous studies showed that the virB operon of B. abortus is tightly regulated within the host cells. In order to identify factors implicated in the control of virB expression, we searched for proteins of Brucella that directly bind to the virB promoter (P virB ). Using different procedures, we isolated a 27-kDa protein that binds specifically to P virB . This protein was identified as HutC, the transcriptional repressor of the histidine utilization (hut) genes. Analyses of virB and hut promoter activity revealed that HutC exerts two different roles: it acts as a coactivator of transcription of the virB operon, whereas it represses the hut genes. Such activities were observed both intracellularly and in bacteria incubated under conditions that resemble the intracellular environment. Electrophoresis mobility shift assays (EMSA) and DNase I footprinting experiments revealed the structure, affinity, and localization of the HutC-binding sites and supported the regulatory role of HutC in both hut and virB promoters. Taken together, these results indicate that Brucella coopted the function of HutC to coordinate the Hut pathway with transcriptional regulation of the virB genes, probably as a way to sense its own metabolic state and develop adaptive responses to overcome intracellular host defenses.Type IV secretion systems (T4SS) are multicomponent machineries central to the pathogenesis of many bacterial genera (e.g., Brucella, Agrobacterium, Helicobacter, Legionella, and Bordetella) (4). T4SS function comprises recognition and translocation of specific substrates across the bacterial cell envelope. The nature of the translocated substrates varies from proteins to DNA-protein complexes. In addition to the wellstudied Agrobacterium transferred DNA (T-DNA) and Bordetella pertussis toxin, several translocated effectors have been identified for Helicobacter, Legionella, and Brucella (7). In every case, the translocated molecules alter cellular processes in such a way that allows the pathogen to overcome host defenses.Brucella is a gram-negative bacterium that causes brucellosis, a worldwide zoonosis that affects domestic mammals. Different Brucella species vary in their host preferences. Brucella abortus, Brucella suis, and Brucella melitensis infect cattle, pigs, and goats, respectively, but also infect humans. In animals, the symptoms of the disease are sterility in males and abortion in pregnant females (6). In humans, brucellosis causes undulant fever during the acute phase and, if it reaches chronicity, can lead to endocarditis, osteoarthritis, and neurological damage.Brucella is an intracellular parasite that persists and replicates within host macrophages. After internalization, the bacterium actively controls the matur...

SUMMARY Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery.