{"id":18177,"date":"2020-01-24T09:45:16","date_gmt":"2020-01-24T08:45:16","guid":{"rendered":"https:\/\/news.embl.de\/?p=18177"},"modified":"2024-03-22T10:56:29","modified_gmt":"2024-03-22T09:56:29","slug":"exploring-how-transcription-factors-work-together","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/exploring-how-transcription-factors-work-together\/","title":{"rendered":"How transcription factors work together"},"content":{"rendered":"\n<p>Researchers in the Zaugg group have developed a statistical learning framework that allows them to study cooperativity between transcription factors, as they report in <em>Nature Communications<\/em>. The results of the study show that cooperativity between transcription factors from different families is mediated by specific DNA sites. This provides an additional regulatory step in DNA transcription.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A large set of possibilities<\/h2>\n\n\n\n<p>\u201cIt often is not just one transcription factor that regulates a gene. They usually act in cooperation,\u201d says group leader Judith Zaugg. The function of transcription factors can vary strongly, depending on the context in which they act. \u201cThe same transcription factor, interacting with another partner, can be involved in a completely different type of disease. Changing the partner will have a functional impact,\u201d Zaugg explains.<\/p>\n\n\n\n<p>Ignacio Ibarra, postdoctoral fellow in the Zaugg group and the main developer of the new framework, used large-scale genomics data from an <em>in vitro <\/em>experiment to predict cooperative binding between pairs of transcription factors. Following up on a specific pair of transcription factor families, Forkhead and Ets, and using data from chronic lymphocytic leukaemia patients, he found that co-expression of these factors allowed patients to be efficiently divided into groups of high and low expression of both transcription factors. High expression levels were associated with later commencement of treatment.<\/p>\n\n\n\n<p>The cooperativity predictions were also validated <em>in vitro<\/em> in collaboration with EMBL\u2019s Hennig group. \u201cIn computational studies, the validation often turns out to be the missing part,\u201d says Zaugg. \u201cThis study is a very nice example of what\u2019s possible thanks to the EMBL environment.\u201d<\/p>\n\n\n\n<p>Although many transcription factors act in pairs, Ibarra explains that the functionality of this pairing has not yet been extensively studied. \u201cThe question now is: how many biological events were missed because the analysis only focused on one transcription factor and not on pairs?\u201d&nbsp;he says. The framework Ibarra has created is a first step towards a larger catalogue of possible transcription factor cooperation functions that can be described with available data.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Dancing at the binding sites<\/h2>\n\n\n\n<p>Ibarra observed that Forkhead\u2013Ets pairs were not in direct contact with each other during their interactions, but connected at the DNA binding site through a protein residue. The dynamics between them reminded Ibarra of two dancers going back and forth, with DNA as the music that determines their movements.<\/p>\n\n\n\n<p>\u201cTranscription factor pairs are far less abundant than single transcription factors when you are observing data, but they are much more interesting,\u201d says Ibarra. \u201cYou could picture a whole orchestra and single dancers, but in the middle of the floor there is a couple dancing that is drawing all the attention.\u201d<\/p>\n\n\n\n<p>Zaugg also likes this analogy, because it describes various aspects of the transcription factor interaction. \u201cIf you have a partner who dances well, you don\u2019t need to dance so well yourself to look good,\u201d says Zaugg. \u201cAnd this is essentially what we found: one of the transcription factors binds very weakly and the other one very strongly, but still their interaction works. But without a partner, this dance is not possible at all.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Wider benefits<\/h2>\n\n\n\n<p>It is planned to make the catalogue developed by the group available as a web service. The Zaugg group has several ongoing projects in which this tool will be valuable, and the huge amount of observable transcription factor interactions means that the scientific community at large will benefit from it. \u201cIt will be an important resource that researchers can use to have a look at their specific system and the specific transcription factors they are working with,\u201d says Zaugg.<\/p>\n\n\n\n<p>The Zaugg group also <a href=\"https:\/\/news.embl.de\/science\/a-classification-tool-for-transcription-factors\/\">recently published diffTF<\/a>, a piece of software that can be used by scientists to classify transcription factors into activators or repressors. \u201cWe are a computational group,\u201d says Zaugg. \u201cWe work on projects that we find biologically interesting, but with a strong focus on computational tools, algorithms, or data generation that will prove useful to other researchers.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL researchers have developed a method to observe interactions between transcription factors<\/p>\n","protected":false},"author":69,"featured_media":18179,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[189,43,539,44,225],"embl_taxonomy":[],"class_list":["post-18177","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-computational-biology","tag-heidelberg","tag-research-highlight","tag-transcription","tag-zaugg"],"acf":{"article_intro":"<p>EMBL researchers have developed a method to observe interactions between transcription factors<\/p>\n","related_links":false,"article_sources":[{"source_description":"<p>Ibarra IL, Hollmann NM, Klaus B, Augsten S, Velten B, Hennig J, Zaugg JB (2020). Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions. <em>Nature Communications<\/em>. DOI:10.1038\/s41467-019-13888-7<\/p>\n","source_link_url":"https:\/\/doi.org\/10.1038\/s41467-019-13888-7"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"field_target_display":"embl","source_article":false,"in_this_article":false,"press_contact":"None"},"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 transcription factors work together | EMBL<\/title>\n<meta name=\"description\" content=\"EMBL researchers in the Zaugg group have developed a statistical learning framework to study cooperativity between transcription factors\" \/>\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\/exploring-how-transcription-factors-work-together\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How transcription factors work together | EMBL\" \/>\n<meta property=\"og:description\" content=\"EMBL researchers in the Zaugg group have developed a statistical learning framework to study cooperativity between transcription factors\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/exploring-how-transcription-factors-work-together\/\" \/>\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=\"2020-01-24T08:45:16+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-22T09:56:29+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/01\/TF-TF-binding_web.jpg\" \/>\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\/jpeg\" \/>\n<meta name=\"author\" content=\"Fabian Oswald\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Fabian Oswald\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 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\/exploring-how-transcription-factors-work-together\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/exploring-how-transcription-factors-work-together\/\"},\"author\":{\"name\":\"Fabian Oswald\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/48be706f1efcc54679ef766039c416ae\"},\"headline\":\"How transcription factors work together\",\"datePublished\":\"2020-01-24T08:45:16+00:00\",\"dateModified\":\"2024-03-22T09:56:29+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/exploring-how-transcription-factors-work-together\/\"},\"wordCount\":660,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/exploring-how-transcription-factors-work-together\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2020\/01\/TF-TF-binding_web.jpg\",\"keywords\":[\"computational biology\",\"heidelberg\",\"research highlight\",\"transcription\",\"zaugg\"],\"articleSection\":[\"Science\",\"Science &amp; 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