Background: Chromatin organization is central to precise control of gene expression. In various eukaryotic species, domains of pervasive cis-chromatin interactions demarcate functional domains of the genomes. In nematode Caenorhabditis elegans, however, pervasive chromatin contact domains are limited to the dosage-compensated sex chromosome, leaving the principle of C. elegans chromatin organization unclear. Transcription factor III C (TFIIIC) is a basal transcription factor complex for RNA polymerase III, and is implicated in chromatin organization. TFIIIC binding without RNA polymerase III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remains unknown. Results: We identified 504 TFIIIC-bound sites absent of RNA polymerase III and TATA-binding protein co-occupancy characteristic of extra-TFIIIC sites in C. elegans embryos. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Extra-TFIIIC sites formed dense clusters in cis. The clusters of extra-TFIIIC sites were highly over-represented within the distal arm domains of the autosomes that presented a high level of heterochromatinassociated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC clusters were embedded in the laminaassociated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions. Conclusion: Clusters of extra-TFIIIC sites were pervasive in the arm domains of C. elegans autosomes, near the outer boundaries of H3K9me3-marked regions. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans.

Viruses, including retroviruses, can be passed from mothers to their progeny during birth and breastfeeding. It is assumed that newborns may develop immune tolerance to milk-transmitted pathogens similarly to food antigens. I/LnJ mice are uniquely resistant to retroviruses acquired as newborns or as adults as they produce virus-neutralizing antibodies (Abs). A loss-of-function allele of H2-Ob (Ob), originally mapped within the virus infectivity controller 1 (vic1) locus is responsible for production of anti-retrovirus Abs in I/LnJ mice. Importantly, Ob deficient and vic1 I/LnJ congenic mice on other genetic backgrounds produce anti-virus Abs when infected as adults, but not as newborns. We report here that I/LnJ mice carry an additional genetic locus, virus infectivity controller 2 (vic2), that abrogates neonatal immune tolerance to retroviruses. Further genetic analysis mapped the vic2 locus to the telomeric end of chromosome 15. Identification of the vic2 gene and understanding of the related signaling pathways would make blocking of neonatal immune tolerance to retroviruses an achievable goal. Importance This work describes a previously unknown genetic mechanism that allows neonates to respond to infections as efficiently as adults

Both viruses and bacteria produce pathogen associated molecular patterns that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.

BACKGROUND: Chromatin organization is central to precise control of gene expression. In vertebrates, the insulator protein CTCF plays a central role in organizing chromatin into topologically associated domains (TADs). In nematode C. elegans, however, a CTCF homolog is absent, and pervasive TAD structures are limited to the dosage-compensated sex chromosome, leaving the 25 principle of C. elegans chromatin organization unclear. Transcription Factor III C (TFIIIC) is a basal transcription factor complex for RNA Polymerase III (Pol III), also implicated in chromatin organization. TFIIIC binding without Pol III co-occupancy, referred to as extra-TFIIIC binding, has been implicated in insulating active and inactive chromatin domains in yeasts, flies, and mammalian cells. Whether extra-TFIIIC sites are present and contribute to chromatin organization in C. elegans remain unknown. 30 RESULTS: We identified, in C. elegans embryos, 504 TFIIIC-bound sites absent of Pol III and TATAbinding protein co-occupancy characteristic of extra-TFIIIC sites. Extra-TFIIIC sites constituted half of all identified TFIIIC binding sites in the genome. Unlike Pol III-associated TFIIIC sites predominantly localized in the sex chromosome, extra-TFIIIC sites were highly over-represented within autosomes. Extra-TFIIIC sites formed dense clusters in cis. The autosomal regions enriched for extra-TFIIIC site 35 clusters presented a high level of heterochromatin-associated histone H3K9 trimethylation (H3K9me3). Furthermore, extra-TFIIIC site clusters were embedded in the lamina-associated domains. Despite the heterochromatin environment of extra-TFIIIC sites, the individual clusters of extra-TFIIIC sites were devoid of and resided near the individual H3K9me3-marked regions. CONCLUSION: Clusters of extra-TFIIIC sites were pervasive near the outer boundaries of H3K9me3-40 marked regions in C. elegans. Given the reported activity of extra-TFIIIC sites in heterochromatin insulation in yeasts, our observation raised the possibility that TFIIIC may also demarcate heterochromatin in C. elegans. 3 BACKGROUND 45 Eukaryotic genomes are organized into domains of various chromatin features including actively transcribed regions, transcription factor-bound regions, and transcriptionally repressed regions [1-4].Demarcation of chromatin domains is central to precise control and memory of gene expression patterns. Several proteins have been proposed to have activity in demarcating chromatin domains by acting as a physical boundary [5,6], generating nucleosome depleted regions [7], mediating long-range 50 chromatin interactions [8,9], or tethering chromatin to the nuclear periphery [10]. Despite intense studies [11][12][13][14][15], how chromatin domains are demarcated remains poorly understood.The genome of nematode Carnorhabditis elegans has served as a model to study chromatin organization [3,[16][17][18]. The highest level of chromatin organization in C. elegans is the chromatin feature that distinguishes between the X chromosome and the autosomes. The X chrom...

Both viruses and bacteria produce “pathogen associated molecular patterns” that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites, while viruses could change the metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of murine leukemia virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus open a new avenue for future investigations.