{"id":1204,"date":"2020-01-08T16:47:00","date_gmt":"2020-01-08T16:47:00","guid":{"rendered":"https:\/\/www.embl.org\/groups\/zaugg\/?p=1204"},"modified":"2022-06-07T16:48:00","modified_gmt":"2022-06-07T16:48:00","slug":"our-paper-on-tf-cooperative-binding-is-out","status":"publish","type":"post","link":"https:\/\/www.embl.org\/groups\/zaugg\/blog\/2020\/01\/our-paper-on-tf-cooperative-binding-is-out\/","title":{"rendered":"Our paper on TF cooperative binding is out!"},"content":{"rendered":"\n<p>Check out <a href=\"https:\/\/www.nature.com\/articles\/s41467-019-13888-7\">here<\/a> how we combine high-throughput genomics data and statistical learning to gain mechanistic insights and functional consequences of cooperative transcription factor binding:<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41467-019-13888-7\">Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions<\/a><\/p>\n\n\n\n<p><a href=\"http:\/\/www.zaugg.embl.de\/data-and-tools\/coop-tf-binding\/\">App, data and code<\/a><\/p>\n\n\n\n<p>Recent high-throughput transcription factor (TF) binding assays revealed that TF cooperativity is a widespread phenomenon. However, a global mechanistic and functional understanding of TF cooperativity is still lacking. To address this, here we introduce a statistical learning framework that provides structural insight into TF cooperativity and its functional consequences based on next generation sequencing data. We identify DNA shape as driver for cooperativity, with a particularly strong effect for Forkhead-Ets pairs. Follow-up experiments reveal a local shape preference at the Ets-DNA-Forkhead interface and decreased cooperativity upon loss of the interaction. Additionally, we discover many functional associations for cooperatively bound TFs. Examination of the link between FOXO1:ETV6 and lymphomas reveals that their joint expression levels improve patient clinical outcome stratification. Altogether, our results demonstrate that inter-family cooperative TF binding is driven by position-specific DNA readout mechanisms, which provides an additional regulatory layer for downstream biological functions.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Check out here how we combine high-throughput genomics data and statistical learning to gain mechanistic insights and functional consequences of cooperative transcription factor binding: Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions&hellip;<\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[8828],"tags":[],"embl_taxonomy":[],"class_list":["post-1204","post","type-post","status-publish","format-standard","hentry","category-new-publication"],"acf":[],"embl_taxonomy_terms":[],"featured_image_src":"https:\/\/www.embl.org\/groups\/zaugg\/wp-includes\/images\/media\/default.svg","_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/posts\/1204","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/comments?post=1204"}],"version-history":[{"count":1,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/posts\/1204\/revisions"}],"predecessor-version":[{"id":1206,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/posts\/1204\/revisions\/1206"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/media?parent=1204"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/categories?post=1204"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/tags?post=1204"},{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/embl_taxonomy?post=1204"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}