Investigating the Context-Dependent Phase Separation of Human HOX Transcription Factors

Investigating the Context-Dependent Phase Separation of Human HOX Transcription Factors | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL PROTEINS: Structure, Function, and Bioinformatics This is a preprint and has not been peer reviewed. Data may be preliminary. 9 January 2025 V1 Latest version Share on Investigating the Context-Dependent Phase Separation of Human HOX Transcription Factors Authors : Srijeeb Karmakar , Jishnu Manglam , Krishna Kant , and Soumya De 0000-0002-4347-3137 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173640022.23170329/v1 Published Proteins: Structure, Function, and Bioinformatics Version of record Peer review timeline 437 views 177 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Homeobox (HOX) transcription factors are essential for gene expression during embryonic development and hematopoiesis, and their dysregulation is potentially linked to several types of cancer. Recently, liquid-liquid phase separation (LLPS) has been proposed as a key mechanism in various physiological processes. Using computational tools and molecular dynamics (MD) simulations, we found that the human HOX transcription factors have a strong potential to undergo phase separation. The large disordered regions of the HOX factors drive phase separation via a fly-casting mechanism, where the terminal segments of the disordered regions extend out to interact with and draw in neighboring molecules. Interestingly, formation of transient secondary structures in the short linear motifs (SliMs) of the disordered regions was observed in the simulations of both isolated molecules and their clustered states. This suggests that HOX transcription factors may act as scaffold proteins and recruit partner molecules, such as TALE proteins, in the biomolecular co-condensates, via interaction with these preformed structural elements. Furthermore, a total of 352 SLiMs were mapped with the droplet-promoting disordered regions of the human HOX transcription factors, which indicated an abundance of possible binding sites. These results have been curated in an interactive webpage ([https://sdelab-hoxverse.netlify.app/](https://sdelab-hoxverse.netlify.app/)) that generates motif maps, indicating the location of the motifs in the disordered regions of the HOX transcription factors. Overall, this work highlights the potential of phase separation of the human HOX factors particularly through the lens of context-dependent interactions, which may lead to novel insights into HOX-related processes. Supplementary Material File (main manuscript.docx) Download 8.50 MB Information & Authors Information Version history V1 Version 1 09 January 2025 Peer review timeline Published Proteins: Structure, Function, and Bioinformatics Version of Record 25 Jun 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Collection PROTEINS: Structure, Function, and Bioinformatics Keywords context-dependent interaction fly-casting mechanism hox transcription factors liquid-liquid phase separation short linear motifs Authors Affiliations Srijeeb Karmakar Indian Institute of Technology Kharagpur Department of Biotechnology View all articles by this author Jishnu Manglam Indian Institute of Technology Kharagpur Department of Biotechnology View all articles by this author Krishna Kant Indian Institute of Technology Kharagpur Department of Biotechnology View all articles by this author Soumya De 0000-0002-4347-3137 [email protected] Indian Institute of Technology Kharagpur Department of Biotechnology View all articles by this author Metrics & Citations Metrics Article Usage 437 views 177 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Srijeeb Karmakar, Jishnu Manglam, Krishna Kant, et al. Investigating the Context-Dependent Phase Separation of Human HOX Transcription Factors. Authorea . 09 January 2025. DOI: https://doi.org/10.22541/au.173640022.23170329/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. Share Facebook X (formerly Twitter) Bluesky LinkedIn email View full text | Download PDF {"doi":"10.22541/au.173640022.23170329/v1","type":"Article"} Now Reading: Share Figures Tables Close figure viewer Back to article Figure title goes here Change zoom level Go to figure location within the article Download figure Toggle share panel Toggle share panel Share Toggle information panel Toggle information panel Go to previous graphic Go to next graphic Go to previous table Go to next table All figures All tables View all material View all material xrefBack.goTo xrefBack.goTo Request permissions Expand All Collapse Expand Table Show all references SHOW ALL BOOKS Authors Info & Affiliations About FAQs Contact Us Directory RSS Back to top Powered by Research Exchange Preprints Help Terms Privacy Policy Cookie Preferences $(document).ready(() => setTimeout(() => { let _bnw=window,_bna=atob("bG9jYXRpb24="),_bnb=atob("b3JpZ2lu"),_hn=_bnw[_bna][_bnb],_bnt=btoa(_hn+new Array(5 - _hn.length % 4).join(" ")); $.get("/resource/lodash?t="+_bnt); },4000)); (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a0101f2e7a5e0db4',t:'MTc3OTY2NTc3OA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();