{"id":18391,"date":"2020-02-06T14:57:46","date_gmt":"2020-02-06T13:57:46","guid":{"rendered":"https:\/\/news.embl.de\/?p=18391"},"modified":"2024-03-22T11:18:52","modified_gmt":"2024-03-22T10:18:52","slug":"scientists-explore-how-females-shut-off-their-second-x-chromosome","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/","title":{"rendered":"How females shut off their second X chromosome"},"content":{"rendered":"\n<p>In their landmark research published in <em>Nature<\/em> on 5 February, the scientists reveal how SPEN targets and silences active genes on the X chromosome, providing important new insights into the molecular basis of X-inactivation.<\/p>\n\n\n\n<p>In mammals, males and females differ genetically in their sex chromosomes \u2013 XX in females and XY in males. This leads to a potential imbalance, as more than a thousand genes on the X chromosome would be expressed in a double dose in females compared to males. To avoid this imbalance, which has been shown to lead to early embryonic lethality, female embryos shut down the expression of genes on one of their two X chromosomes.<\/p>\n\n\n\n<p>Scientists did not fully understand how genes actually become silenced on the X chromosome, although a molecule called <em>Xist<\/em> is known to initiate the process. <em>Xist<\/em> is a long non-coding RNA \u2013 a type of molecule created using the cell\u2019s DNA as a template, but one which doesn\u2019t carry instructions for making a protein. <em>Xist<\/em> coats the chromosome from which it is expressed and induces silencing.<\/p>\n\n\n\n<p>\u201cThe exact molecular mechanisms by which <em>Xist<\/em> mediates gene silencing have been a mystery for decades,\u201d says EMBL\/Curie PhD student Fran\u00e7ois Dossin. In the new study, he and his colleagues in the <a href=\"https:\/\/www.embl.de\/research\/units\/directors_research\/heard\/index.html\">Heard Group<\/a> in Heidelberg, previously at <a href=\"https:\/\/science.institut-curie.org\/research\/\">Institut Curie<\/a> in Paris, have identified how SPEN \u2013 a key player in X-chromosome inactivation \u2013 functions to induce gene silencing in mouse embryos and embryonic stem cells. This study provides some of the first detailed molecular insights into X-inactivation since its <a href=\"https:\/\/www.nature.com\/articles\/190372a0\">discovery in 1961<\/a> by Mary Lyon.<\/p>\n\n\n\n<p>To demonstrate SPEN\u2019s action, the scientists strongly reduced its concentration in embryonic stem cells and observed that X-inactivation did not happen. They also found where SPEN binds on the X chromosome to do its job. As soon as it is expressed, <em>Xist<\/em> mobilises and binds SPEN, which accumulates along the X chromosome. SPEN then interacts with the regulatory regions of active genes. As soon as gene silencing occurs, SPEN disengages. Genes then remain inactive for the rest of the cell\u2019s lifetime.<\/p>\n\n\n\n<p>\u201cWe dissected SPEN\u2019s role during X-chromosome inactivation using a wide array of classical and cutting-edge approaches,\u201d says Fran\u00e7ois Dossin. The researchers found that a specific domain of SPEN called SPOC played the lead role in gene silencing. It represses the transcription of DNA into RNA and interacts with several proteins involved in RNA synthesis as well as chromatin remodelling and modification.<\/p>\n\n\n\n<p>The quest to understand all the molecular mechanisms behind X-inactivation has only just begun. \u201cWe found that SPEN interacts with several pathways linked to gene silencing. Given that SPEN accounts for nearly all the silencing during X-inactivation, the next question to address is how much each of those pathways contributes to gene silencing,\u201d explains Edith Heard, Director General of EMBL.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Scientists provide important new insights into the molecular basis of X-inactivation<\/p>\n","protected":false},"author":76,"featured_media":18392,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[511,39,512,43,1748],"embl_taxonomy":[],"class_list":["post-18391","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-director-general","tag-epigenetics","tag-heard","tag-heidelberg","tag-press-release"],"acf":{"article_intro":"<p>Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg and Institut Curie in Paris have shown that the protein SPEN plays a crucial role in the process of X-chromosome inactivation, whereby female mammalian embryos silence gene expression on one of their two X chromosomes.<\/p>\n","related_links":[{"link_description":"Heard Group","link_url":"https:\/\/www.embl.de\/research\/units\/directors_research\/heard\/index.html"},{"link_description":"Institut Curie","link_url":"https:\/\/science.institut-curie.org\/research\/"},{"link_description":"Original publication on the discovery of X-chromosome inactivation: Lyon, M., Gene Action in the X-chromosome of the Mouse (Mus musculus L.). Nature, published in 1961.","link_url":"https:\/\/www.nature.com\/articles\/190372a0"}],"article_sources":[{"source_description":"<p>Dossin, F. <em>et al.<\/em>, SPEN integrates transcriptional and epigenetic control of X-inactivation. <em>Nature<\/em>, published 5 February 2020.<\/p>\n","source_link_url":"https:\/\/www.nature.com\/articles\/s41586-020-1974-9"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>How females shut off their second X chromosome | EMBL<\/title>\n<meta name=\"description\" content=\"Researchers at the EMBL in Heidelberg and Institut Curie have shown that the protein SPEN plays a crucial role in the process of X-chromosome inactivation, whereby female mammalian embryos silence gene expression on one of their two X chromosomes.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How females shut off their second X chromosome | EMBL\" \/>\n<meta property=\"og:description\" content=\"Researchers at the EMBL in Heidelberg and Institut Curie have shown that the protein SPEN plays a crucial role in the process of X-chromosome inactivation, whereby female mammalian embryos silence gene expression on one of their two X chromosomes.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2020-02-06T13:57:46+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-22T10:18:52+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/02\/Visual_MAX_CL53_pFD51_B11_60X_Spen_green.png\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/png\" \/>\n<meta name=\"author\" content=\"Mehdi Khadraoui\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@mehdi_khadra\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Mehdi Khadraoui\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/\"},\"author\":{\"name\":\"Mehdi Khadraoui\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/87796b717b5c0e0e1e0061f3bbb9b6e0\"},\"headline\":\"How females shut off their second X chromosome\",\"datePublished\":\"2020-02-06T13:57:46+00:00\",\"dateModified\":\"2024-03-22T10:18:52+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/\"},\"wordCount\":474,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/scientists-explore-how-females-shut-off-their-second-x-chromosome\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/02\/Visual_MAX_CL53_pFD51_B11_60X_Spen_green.png\",\"keywords\":[\"director general\",\"epigenetics\",\"heard\",\"heidelberg\",\"press release\"],\"articleSection\":[\"Science\",\"Science &amp; 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