{"id":834,"date":"2022-06-02T15:51:25","date_gmt":"2022-06-02T15:51:25","guid":{"rendered":"https:\/\/www.embl.org\/groups\/zaugg\/?page_id=834"},"modified":"2023-05-17T12:17:32","modified_gmt":"2023-05-17T12:17:32","slug":"coop-tf-binding","status":"publish","type":"page","link":"https:\/\/www.embl.org\/groups\/zaugg\/data-and-tools\/coop-tf-binding\/","title":{"rendered":"Resources: Mechanistic insights into transcription factor cooperativity and its impact on protein-phenotype interactions"},"content":{"rendered":"\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\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Explore TF-TF and phenotype associations in <a href=\"https:\/\/coop-tf-binding.herokuapp.com\/\">Cloud App<\/a><\/strong><\/li>\n\n\n\n<li><strong>Source code available here <a href=\"https:\/\/git.embl.de\/rio\/coop-tf-binding\">GitHub repository<\/a><\/strong><\/li>\n\n\n\n<li><strong>Relevant git input and output data:<\/strong>\n<ul class=\"wp-block-list\">\n<li>Processed CAP-SELEX data (<em>k<\/em>-mer\u00a0enrichments).\n<ul class=\"wp-block-list\">\n<li>Files are divided into multiple directories of ca. ~80MB each). You can download them them all with this bash script <a href=\"https:\/\/www.embl.de\/download\/zaugg\/rio\/download_processed_selex_data.sh\">download<\/a><\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>In vivo motif TF-TF <em>k<\/em>-mer motif mapping in [~5-10GB each file]\n<ul class=\"wp-block-list\">\n<li>ChIP-seq peaks <a href=\"https:\/\/www.embl.de\/download\/zaugg\/rio\/motifs_invivo_TF-TF_remap.tar.gz\">ReMap<\/a><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Ontology Association Probabilities for all studied TF-TF terms and terms in this work .\n<ul class=\"wp-block-list\">\n<li>All predictions (including negatives) <a href=\"https:\/\/www.embl.de\/download\/zaugg\/rio\/OAP_all.tar.gz\">download<\/a><\/li>\n\n\n\n<li>Explore <a href=\"https:\/\/coop-tf-binding.herokuapp.com\/\">Cloud App<\/a><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<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&hellip;<\/p>\n","protected":false},"author":10,"featured_media":0,"parent":816,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"embl_taxonomy":[],"class_list":["post-834","page","type-page","status-publish","hentry"],"acf":[],"embl_taxonomy_terms":[],"_links":{"self":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/pages\/834","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/users\/10"}],"replies":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/comments?post=834"}],"version-history":[{"count":3,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/pages\/834\/revisions"}],"predecessor-version":[{"id":7762,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/pages\/834\/revisions\/7762"}],"up":[{"embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/pages\/816"}],"wp:attachment":[{"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/media?parent=834"}],"wp:term":[{"taxonomy":"embl_taxonomy","embeddable":true,"href":"https:\/\/www.embl.org\/groups\/zaugg\/wp-json\/wp\/v2\/embl_taxonomy?post=834"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}