{"id":49659,"date":"2016-08-02T00:00:00","date_gmt":"2016-08-01T23:00:00","guid":{"rendered":"http:\/\/www.pcb.ub.edu\/two-proteins-safeguard-skin-stem-cells\/"},"modified":"2020-11-18T14:56:30","modified_gmt":"2020-11-18T13:56:30","slug":"two-proteins-safeguard-skin-stem-cells","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/two-proteins-safeguard-skin-stem-cells\/","title":{"rendered":"Two proteins safeguard skin stem cells"},"content":{"rendered":"<p>The proteins identified,\u00a0Dnmt3a y Dnmt3b, are crucial for the self-renewal of skin stem cells as they trigger the first step of the genetic programme of these cells.\u00a0\u201cWithout them, this programme is not activated and the stem cells collapse and disappear from the tissue,\u201dexplains\u00a0Salvador Aznar Benitah, head of the\u00a0<a href=\"http:\/\/www.irbbarcelona.org\/en\/research\/stem-cells-and-cancer\" target=\"_blank\" rel=\"noopener noreferrer\">Stem Cells and Cancer<\/a>\u00a0lab at IRB Barcelona.<\/p>\n<p>Lorenzo Rinaldi, a \u201cla Caixa\u201d PhD student and first author of the study, has identified all the regions of the genome that harbour these proteins.\u00a0Rinaldi\u00a0has observed that\u00a0these two proteins exert their activity on gene enhancers and superenhancers\u2014regions far away from the genes that can increase gene transcription speed up to 200-fold\u2014among other regions.<\/p>\n<p>\u201cIt was surprising to see that two proteins that have always been associated with gene repression through DNA methylation are activated in the most transcriptionally active regions of stem cells.\u00a0We had never observed this activity because we were unable to study the global distribution of Dnmt3a and Dnmt3b at the genomic level. Thanks to advances in sequencing techniques, more researchers are observing the very mechanism that we have described,\u201d explains\u00a0Rinaldi.<\/p>\n<p>Of the 12,000 gene enhancers in the genome, about 300 are superenhancers related to stem cells. The two proteins exert their function in these regions in order to trigger the approx. 1,000 genes required for the self-renewing capacity of stem cells. By methylating the superenhancer, these proteins trigger the first step of the machinery that leads to the amplified expression of these essential genes for the stem cell.<\/p>\n<p>\n<strong>Link to cancer<\/strong><\/p>\n<p>There are various features related to\u00a0cancer cells. Among these, first, these cells\u00a0show altered DNA methylation. Second,\u00a0gene enhancers are highly mutated, not only in the bodies of the genes themselves. These observations have been made possible thanks to mass sequencing of tumour cell genomes. Third, these\u00a0two proteins, Dnmt3a and Dnmt3b, are altered in many types of tumour, such as those encountered in leukaemia, the lung, and the colon.<\/p>\n<p>\u201cEach of these three components is associated with the development of various kinds of cancer. Given that these proteins activate gene expression enhancers through DNA methylation, we believe that it would be of interest to study them in cancer cells in order to determine whether they participate in tumour development,\u201d\u00a0concludes Dr. Aznar Benitah.<\/p>\n<p style=\"font-family: heuristicaregular, arial, sans-serif;font-size: 15px;line-height: 22px\">The study has been funded by the Spanish Ministry of Economy and Competitiveness and ERDFs. Dr. Aznar Benitah\u2019s lab is also supported by The European Council for Research (ERC), the Worldwide Cancer Research Foundation, the\u00a0<em>Fundaci\u00f3 Marat\u00f3 de TV3<\/em>, the\u00a0<em>Fundaci\u00f3n Vencer el C\u00e1ncer<\/em>, the\u00a0<em>Fundaci\u00f3n Bot\u00edn<\/em>\u00a0and the Government of Catalonia.<br \/>\n\u00a0<\/p>\n<p><strong>\u2022\u00a0Reference article<\/strong>:\u00a0Lorenzo Rinaldi, Debayan Datta, Judit Serrat, Lluis Morey, Guiomar Solanas, Alexandra Avgustinova, Enrique Blanco, Jos\u00e9 Ignacio Pons, David Gomez Matallanas, \u00a0Alex Von Kriegsheim, Luciano Di Croce\u00a0and Salvador Aznar Benitah.\u00a0<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27476967\" target=\"_blank\" rel=\"noopener noreferrer\">&#8220;Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis&#8221;<\/a>.\u00a0Cell Stem Cell\u00a0(28 July 2016). Doi: 10.1016\/j.stem.2016.06.020\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A study led by ICREA researcher\u00a0Salvador Aznar Benitah\u00a0and undertaken at the Institute for Research in Biomedicine (<a href=\"http:\/\/www.pcb.ub.edu\/portal\/en\/cerca?p_p_id=cercador_WAR_empleatsempresesportlet&amp;p_p_lifecycle=0&amp;p_p_state=maximized&amp;p_p_mode=view&amp;p_p_col_id=column-1&amp;p_p_col_count=1&amp;_cercador_WAR_empleatsempresesportlet_jspPage=%2Fhtml%2Fcommon%2Fdetall-empresa.jsp&amp;_cercador_WAR_empleatsempresesportlet_empresaId=ENT_000001&amp;_cercador_WAR_empleatsempresesportlet_redirect=%2Fportal%2Fca%2Fcerca%3Fp_p_id%3Dcercador_WAR_empleatsempresesportlet%26p_p_lifecycle%3D0%26p_p_mode%3Dview%26_cercador_WAR_empleatsempresesportlet_keywords%3Dirb%26_cercador_WAR_empleatsempresesportlet_tab%3D1\" target=\"_blank\" rel=\"noopener noreferrer\">IRB Barcelona<\/a>) based at PCB\u00a0has identified\u00a0two proteins that are fundamental to conserve skin stem cells\u00a0and has shown that without these proteins these cells are lost. The study, which has been published in\u00a0Cell Stem Cell,\u00a0has involved Luciano Di Croce\u2019s group at the Center for Genomic Regulation (CRG).<\/p>\n<p>\u00a0<\/p>\n","protected":false},"author":1,"featured_media":53766,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"class_list":["post-49659","post","type-post","status-publish","format-standard","has-post-thumbnail","category-uncategorized"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Two proteins safeguard skin stem cells - Parc Cient\u00edfic de Barcelona<\/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:\/\/www.pcb.ub.edu\/en\/two-proteins-safeguard-skin-stem-cells\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Two proteins safeguard skin stem cells - Parc Cient\u00edfic de Barcelona\" \/>\n<meta property=\"og:description\" content=\"A study led by ICREA researcher\u00a0Salvador Aznar Benitah\u00a0and undertaken at the Institute for Research in Biomedicine (IRB Barcelona) based at PCB\u00a0has identified\u00a0two proteins that are fundamental to conserve skin stem cells\u00a0and has shown that without these proteins these cells are lost. 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