{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:29:25Z","timestamp":1790972965074,"version":"4.1.0"},"posted":{"date-parts":[[2024,9,29]]},"reference-count":92,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 1551 Project No. 464588647"],"award-info":[{"award-number":["SFB 1551 Project No. 464588647"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["10001070"],"award-info":[{"award-number":["10001070"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["320030-227954"],"award-info":[{"award-number":["320030-227954"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Research Council","award":["743312"],"award-info":[{"award-number":["743312"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P40 OD010440"],"award-info":[{"award-number":["P40 OD010440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Novartis","award":["20C236"],"award-info":[{"award-number":["20C236"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  In differentiated cells, genome segregation into heterochromatin and euchromatin is mediated by modified histones, which recruit so-called reader proteins. Surprisingly, many histone modifiers remain functional in the absence of catalytic activity, but the underlying mechanism remains unclear. To explore this puzzle, we examined the relationship between\n                  <jats:italic>C. elegans<\/jats:italic>\n                  MET-2\/SETDB1, a histone H3 lysine (H3K9me) methyltransferase that also has non-catalytic roles, and the canonical H3K9me reader HPL-2 (HP1). We show that HPL-2 represses transcription and supports organogenesis independently of H3K9me binding, whereas complete loss of\n                  <jats:italic>met-2<\/jats:italic>\n                  and\n                  <jats:italic>hpl-2<\/jats:italic>\n                  causes severe transcriptional and developmental defects. MET-2 and HPL-2 rely on different binding partners - the disordered protein LIN-65\/ATF7IP and the multi-zinc finger protein LIN-13, respectively \u2013 for localization and function. The results suggest that HPL-2 can operate through alternative protein interactions, and that HPL-2 and MET-2 function in parallel, H3K9me-independent pathways, with H3K9me acting as a reinforcing but non-essential contributor to these processes.\n                <\/jats:p>","DOI":"10.1101\/2024.09.29.615660","type":"posted-content","created":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T23:10:11Z","timestamp":1727651411000},"source":"Crossref","is-referenced-by-count":4,"title":["HPL-2\/HP1 and MET-2\/SETDB1 bind distinct co-factors that promote heterochromatic foci, gene repression and organogenesis independently of H3K9 methylation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-6973","authenticated-orcid":false,"given":"Colin E.","family":"Delaney","sequence":"first","affiliation":[{"name":"University of Basel Biozentrum, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Fol","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology (IMB), Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1151-8125","authenticated-orcid":false,"given":"Jia Emil","family":"You","sequence":"additional","affiliation":[{"name":"University of Basel Biozentrum, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan B.","family":"Gruenewald","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology, Johannes Gutenberg University Mainz, Mainz, Germany"},{"name":"KOMET1, Institute of Physics, Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Ferrario","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology (IMB), Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3610-9123","authenticated-orcid":false,"given":"Susan M.","family":"Gasser","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland"},{"name":"Fondation ISREC, Agora Cancer Research Center, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Moeckel","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology (IMB), Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Stelzl","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology (IMB), Mainz, Germany"},{"name":"Institute for Quantitative and Computational Biosciences (IQCB), Johannes Gutenberg University Mainz, Germany"},{"name":"Institute of Molecular Physiology, Johannes Gutenberg University Mainz, Mainz, Germany"},{"name":"KOMET1, Institute of Physics, Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-0946","authenticated-orcid":false,"given":"Jan","family":"Padeken","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biology (IMB), Mainz, Germany"},{"name":"Institute for Quantitative and Computational Biosciences (IQCB), Johannes Gutenberg University Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-3237","authenticated-orcid":false,"given":"Susan E.","family":"Mango","sequence":"additional","affiliation":[{"name":"University of Basel Biozentrum, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062611401719000_2024.09.29.615660v5.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.03.001"},{"key":"2026062611401719000_2024.09.29.615660v5.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00483-w"},{"key":"2026062611401719000_2024.09.29.615660v5.3","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0833"},{"key":"2026062611401719000_2024.09.29.615660v5.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03520-4"},{"key":"2026062611401719000_2024.09.29.615660v5.5","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2017.1279604"},{"key":"2026062611401719000_2024.09.29.615660v5.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0583"},{"key":"2026062611401719000_2024.09.29.615660v5.7","doi-asserted-by":"crossref","first-page":"103982","DOI":"10.1016\/j.drudis.2024.103982","article-title":"SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer","volume":"29","year":"2024","journal-title":"Drug Discov Today"},{"key":"2026062611401719000_2024.09.29.615660v5.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1356"},{"key":"2026062611401719000_2024.09.29.615660v5.9","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-020-00663-y"},{"key":"2026062611401719000_2024.09.29.615660v5.10","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-022-00453-8"},{"key":"2026062611401719000_2024.09.29.615660v5.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature12032"},{"key":"2026062611401719000_2024.09.29.615660v5.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.05.009"},{"key":"2026062611401719000_2024.09.29.615660v5.13","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg306"},{"key":"2026062611401719000_2024.09.29.615660v5.14","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf194"},{"key":"2026062611401719000_2024.09.29.615660v5.15","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abk0793"},{"key":"2026062611401719000_2024.09.29.615660v5.16","doi-asserted-by":"publisher","DOI":"10.1016\/J.MOLCEL.2020.02.005"},{"key":"2026062611401719000_2024.09.29.615660v5.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature22822"},{"key":"2026062611401719000_2024.09.29.615660v5.18","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E24-01-0046"},{"key":"2026062611401719000_2024.09.29.615660v5.19","doi-asserted-by":"crossref","unstructured":"A. N. McMurchy et al., Correction: A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress. Elife 6 (2017).","DOI":"10.7554\/eLife.32516"},{"key":"2026062611401719000_2024.09.29.615660v5.20","doi-asserted-by":"publisher","DOI":"10.1101\/gr.180489.114"},{"key":"2026062611401719000_2024.09.29.615660v5.21","doi-asserted-by":"publisher","DOI":"10.1242\/dev.009373"},{"key":"2026062611401719000_2024.09.29.615660v5.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.09.035"},{"key":"2026062611401719000_2024.09.29.615660v5.23","doi-asserted-by":"publisher","DOI":"10.1101\/gad.322495.118"},{"key":"2026062611401719000_2024.09.29.615660v5.24","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3672"},{"key":"2026062611401719000_2024.09.29.615660v5.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-021-00712-4"},{"key":"2026062611401719000_2024.09.29.615660v5.26","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201811038"},{"key":"2026062611401719000_2024.09.29.615660v5.27","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat6224"},{"key":"2026062611401719000_2024.09.29.615660v5.28","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948297"},{"key":"2026062611401719000_2024.09.29.615660v5.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.04.474"},{"key":"2026062611401719000_2024.09.29.615660v5.30","doi-asserted-by":"crossref","unstructured":"T. Patel , O. Hobert , Coordinated control of terminal differentiation and restriction of cellular plasticity. Elife 6 (2017).","DOI":"10.7554\/eLife.24100"},{"key":"2026062611401719000_2024.09.29.615660v5.31","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf051"},{"key":"2026062611401719000_2024.09.29.615660v5.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00776-w"},{"key":"2026062611401719000_2024.09.29.615660v5.33","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81645-1"},{"key":"2026062611401719000_2024.09.29.615660v5.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.09.049"},{"key":"2026062611401719000_2024.09.29.615660v5.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.04.023"},{"key":"2026062611401719000_2024.09.29.615660v5.36","doi-asserted-by":"publisher","DOI":"10.1101\/gad.344234.120"},{"key":"2026062611401719000_2024.09.29.615660v5.37","doi-asserted-by":"publisher","DOI":"10.1101\/gad.559610"},{"key":"2026062611401719000_2024.09.29.615660v5.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.051"},{"key":"2026062611401719000_2024.09.29.615660v5.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.066"},{"key":"2026062611401719000_2024.09.29.615660v5.40","doi-asserted-by":"crossref","unstructured":"A. Poleshko et al., H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. Elife 8 (2019).","DOI":"10.7554\/eLife.49278"},{"key":"2026062611401719000_2024.09.29.615660v5.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069473"},{"key":"2026062611401719000_2024.09.29.615660v5.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523402113"},{"key":"2026062611401719000_2024.09.29.615660v5.43","doi-asserted-by":"publisher","DOI":"10.1242\/dev.059501"},{"key":"2026062611401719000_2024.09.29.615660v5.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002418"},{"key":"2026062611401719000_2024.09.29.615660v5.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002542"},{"key":"2026062611401719000_2024.09.29.615660v5.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-019-0193-2"},{"key":"2026062611401719000_2024.09.29.615660v5.47","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar7366"},{"key":"2026062611401719000_2024.09.29.615660v5.48","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.2c00210"},{"key":"2026062611401719000_2024.09.29.615660v5.49","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.056465"},{"key":"2026062611401719000_2024.09.29.615660v5.50","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(89)90158-3"},{"key":"2026062611401719000_2024.09.29.615660v5.51","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/155.3.1127"},{"key":"2026062611401719000_2024.09.29.615660v5.52","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/164.1.135"},{"key":"2026062611401719000_2024.09.29.615660v5.53","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600088"},{"key":"2026062611401719000_2024.09.29.615660v5.54","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063127"},{"key":"2026062611401719000_2024.09.29.615660v5.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.05.029"},{"key":"2026062611401719000_2024.09.29.615660v5.56","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1514"},{"key":"2026062611401719000_2024.09.29.615660v5.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00542-6"},{"key":"2026062611401719000_2024.09.29.615660v5.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.09.002"},{"key":"2026062611401719000_2024.09.29.615660v5.59","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf2687"},{"key":"2026062611401719000_2024.09.29.615660v5.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.12.004"},{"key":"2026062611401719000_2024.09.29.615660v5.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.09.005"},{"key":"2026062611401719000_2024.09.29.615660v5.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.04.018"},{"key":"2026062611401719000_2024.09.29.615660v5.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108315"},{"key":"2026062611401719000_2024.09.29.615660v5.64","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.192"},{"key":"2026062611401719000_2024.09.29.615660v5.65","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.stemcr.2023.08.004","article-title":"A functional crosstalk between the H3K9 methylation writers and their reader HP1 in safeguarding embryonic stem cell identity","volume":"18","year":"2023","journal-title":"Stem Cell Reports"},{"key":"2026062611401719000_2024.09.29.615660v5.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.037"},{"key":"2026062611401719000_2024.09.29.615660v5.67","doi-asserted-by":"crossref","unstructured":"B. R. Sabari et al., Coactivator condensation at super-enhancers links phase separation and gene control. Science 361 (2018).","DOI":"10.1126\/science.aar3958"},{"key":"2026062611401719000_2024.09.29.615660v5.68","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00127-z"},{"key":"2026062611401719000_2024.09.29.615660v5.69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003061"},{"key":"2026062611401719000_2024.09.29.615660v5.70","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.13109"},{"key":"2026062611401719000_2024.09.29.615660v5.71","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022923508198"},{"key":"2026062611401719000_2024.09.29.615660v5.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.01.002"},{"key":"2026062611401719000_2024.09.29.615660v5.73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162371699"},{"key":"2026062611401719000_2024.09.29.615660v5.74","doi-asserted-by":"publisher","DOI":"10.2174\/13892029113149990002"},{"key":"2026062611401719000_2024.09.29.615660v5.75","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80204-X"},{"key":"2026062611401719000_2024.09.29.615660v5.76","doi-asserted-by":"publisher","DOI":"10.1101\/gad.973302"},{"key":"2026062611401719000_2024.09.29.615660v5.77","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.7"},{"key":"2026062611401719000_2024.09.29.615660v5.78","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01382-2"},{"key":"2026062611401719000_2024.09.29.615660v5.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.032"},{"key":"2026062611401719000_2024.09.29.615660v5.80","doi-asserted-by":"publisher","DOI":"10.1038\/nature22989"},{"key":"2026062611401719000_2024.09.29.615660v5.81","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000644"},{"key":"2026062611401719000_2024.09.29.615660v5.82","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948296"},{"key":"2026062611401719000_2024.09.29.615660v5.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.050"},{"key":"2026062611401719000_2024.09.29.615660v5.84","doi-asserted-by":"crossref","unstructured":"R. S. Kamath , M. Martinez-Campos , P. Zipperlen , A. G. Fraser , J. Ahringer , Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol 2, RESEARCH0002 (2001).","DOI":"10.1186\/gb-2000-2-1-research0002"},{"key":"2026062611401719000_2024.09.29.615660v5.85","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00579-5"},{"key":"2026062611401719000_2024.09.29.615660v5.86","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.120.303564"},{"key":"2026062611401719000_2024.09.29.615660v5.87","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-28549-8_7"},{"key":"2026062611401719000_2024.09.29.615660v5.88","doi-asserted-by":"crossref","unstructured":"G. Raiymbek et al., An H3K9 methylation-dependent protein interaction regulates the non-enzymatic functions of a putative histone demethylase. Elife 9 (2020).","DOI":"10.7554\/eLife.53155"},{"key":"2026062611401719000_2024.09.29.615660v5.89","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-9-9"},{"key":"2026062611401719000_2024.09.29.615660v5.90","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.236"},{"key":"2026062611401719000_2024.09.29.615660v5.91","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAD347"},{"key":"2026062611401719000_2024.09.29.615660v5.92","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.5b00996"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.09.29.615660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T18:40:32Z","timestamp":1782499232000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.09.29.615660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,29]]},"references-count":92,"URL":"https:\/\/doi.org\/10.1101\/2024.09.29.615660","relation":{},"subject":[],"published":{"date-parts":[[2024,9,29]]},"subtype":"preprint"}}