{"id":77,"date":"2012-09-13T13:33:20","date_gmt":"2012-09-13T12:33:20","guid":{"rendered":"http:\/\/blogs.lshtm.ac.uk\/alsfordlab\/?p=77"},"modified":"2014-11-26T11:30:41","modified_gmt":"2014-11-26T10:30:41","slug":"latest-work-on-histone-chaperones-and-vsg-es-regulation-published-in-nucleic-acids-research","status":"publish","type":"post","link":"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2012\/09\/13\/latest-work-on-histone-chaperones-and-vsg-es-regulation-published-in-nucleic-acids-research\/","title":{"rendered":"Latest work on histone chaperones and VSG ES regulation published in Nucleic Acids Research."},"content":{"rendered":"<p><strong>Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in <em>Trypanosoma brucei<\/em>.<\/strong> <em>Nucleic Acids Res<\/em>. (<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22941664\">PubMed<\/a> | <a href=\"http:\/\/nar.oxfordjournals.org\/content\/40\/20\/10150.full.pdf+html\">PDF<\/a>)<\/p>\n<p>A longstanding mystery in <em>T. brucei<\/em> biology is how these parasites are able to express a single variant surface glycoprotein (VSG) from a single sub-telomeric expression site (ES), while repressing at least 14 others. While we cannot claim to have solved this mystery, we have added weight to the contention that chromatin is a key, though probably not the only, player in this process.<\/p>\n<p>We&#8217;ve demonstrated that the histone chaperones, CAF-1b and ASF1A, contribute to the maintenance of silent VSG ESs in <em>T. brucei<\/em>. RNAi depletion of either of these histone chaperones leads to de-repression of the ES promoter, in a cell cycle dependent manner; ASF1A loss led to ES promoter de-repression throughout the cell cycle, while CAF-1b loss resulted in greater de-repression in S and G2\/M phases, due to nucleosome depletion. As has been reported for other factors involved in ES silencing, we didn&#8217;t see any significant readthrough to the ~50kb distal <em>VSG<\/em> gene following chaperone depletion; indeed, we saw the same ES promoter de-repression without readthrough when we depleted the cells for histone H3 (a core histone), suggesting that, though chromatin is clearly important to ES silencing, another layer of control exists.<\/p>\n<p>This adds to the weight of evidence for the importance of chromatin in the maintenance <em>VSG<\/em> expression site silencing &#8211; fundamental to the effective monoallelic expression of this abundant family of <em>T. brucei<\/em> variant surface molecules. This work follows on from that of a number of other groups highlighting a multitude of expression site-influencing chromatin factors, including telomere binding proteins, histone deacetylases, other histone chaperones and components of the nuclear lamina (references below).<\/p>\n<p>DuBois et al (2012) <em>PLoS Biol.<\/em> <strong>10<\/strong>:e1001287<br \/>\nNarayanan et al (2011) <em>Nucleic Acids Res.<\/em> <strong>39<\/strong>:2018-31<br \/>\nStanne et al (2011)<em> Eukaryot. Cell<\/em>\u00a0<strong>10<\/strong>:964-76<br \/>\nWang et al (2010) <em>Mol. Microbiol.<\/em>\u00a0<strong>77<\/strong>:1237-45<br \/>\nDenninger et al (2010) <em>Mol. Microbiol.<\/em> <strong>78<\/strong>:459-74<br \/>\nYang et al (2009) <em>Cell<\/em> (2009) <strong>137<\/strong>:99-109<br \/>\nFigueiredo et al (2008) <em>PLoS Biol.<\/em> <strong>6<\/strong>:e161<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b&#8230;<\/p>\n","protected":false},"author":116,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[12450],"tags":[],"class_list":["post-77","post","type-post","status-publish","format-standard","hentry","category-publication","odd"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Latest work on histone chaperones and VSG ES regulation published in Nucleic Acids Research. - Alsford Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.lshtm.ac.uk\/alsfordlab\/2012\/09\/13\/latest-work-on-histone-chaperones-and-vsg-es-regulation-published-in-nucleic-acids-research\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Latest work on histone chaperones and VSG ES regulation published in Nucleic Acids Research. - 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