Kurdistani, S. | bioRxiv Science

bioRxiv2017

Histone demethylation and c-MYC activation enhance translational capacity in response to amino acid restriction

Nutrient limitation may elicit adaptive epigenetic changes but the nature and mechanisms of the cellular response to specific nutrient deficiencies are incompletely understood. We report that depriving human cells of amino acids (AAs) induces specific loss of H4K20me1 from gene bodies and elevated binding of c-MYC at promoters genome-wide. These effects are most pronounced at ribosomal protein and translation initiation genes, which are upregulated, leading to enhanced protein synthetic capacity. Combination of H4K20 methyltransferase depletion and c-MYC over-expression in rich media is required and sufficient to recapitulate the effects of AA restriction. Our data reveal an unexpected and epigenetically implemented increase in translational capacity when AAs are limiting, likely to safeguard the proteome by making effective use of limited resources.\n\nOne Sentence Summary: Combination of H4K20me1 demethylation and c-MYC activation enhance translational capacity in response to amino acid restriction.

molecular biology↗

bioRxiv2017

Specific Virus-Host Genome Interactions Revealed By Tethered Chromosome Conformation Capture

Viruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1-3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.

microbiology↗