{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:58:36Z","timestamp":1781107116840,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"37","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM131845"],"award-info":[{"award-number":["R35 GM131845"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,9,13]]},"abstract":"<jats:p>\n                    Organisms that count X-chromosome number to determine sex utilize dosage compensation mechanisms to balance X-gene expression between sexes. Typically, a regulatory complex is recruited to X chromosomes of one sex to modulate gene expression. A major challenge is to determine the mechanisms that target regulatory complexes specifically to X. Here, we identify critical X-sequence motifs in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    that act synergistically in hermaphrodites to direct X-specific recruitment of the dosage compensation complex (DCC), a condensin complex. We find two DNA motifs that collaborate with a previously defined 12-bp motif called MEX (motif enriched on X) to mediate binding: MEX II, a 26-bp X-enriched motif and Motif C, a 9-bp motif that lacks X enrichment. Inserting both MEX and MEX II into a new location on X creates a DCC binding site equivalent to an endogenous recruitment site, but inserting only MEX or MEX II alone does not. Moreover, mutating MEX, MEX II, or Motif C in endogenous recruitment sites with multiple different motifs dramatically reduces DCC binding in\u00a0vivo to nearly the same extent as mutating all motifs. Changing the orientation or spacing of motifs also reduces DCC binding. Hence, synergy in DCC binding via combinatorial clustering of motifs triggers DCC assembly specifically on X chromosomes. Using an in\u00a0vitro DNA binding assay, we refine the features of motifs and flanking sequences that are critical for DCC binding. Our work reveals general principles by which regulatory complexes can be recruited across an entire chromosome to control its gene expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2211642119","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T13:57:56Z","timestamp":1662472676000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["Combinatorial clustering of distinct DNA motifs directs synergistic binding of\n                    <i>Caenorhabditis elegans<\/i>\n                    dosage compensation complex to X chromosomes"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-2329","authenticated-orcid":false,"given":"Nicholas J.","family":"Fuda","sequence":"first","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4562-6109","authenticated-orcid":false,"given":"Katju\u0161a","family":"Brejc","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Kruesi","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Ralston","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Bigley","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Shin","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-8554","authenticated-orcid":false,"given":"Miki","family":"Okada","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6530-4588","authenticated-orcid":false,"given":"Barbara J.","family":"Meyer","sequence":"additional","affiliation":[{"name":"HHMI, University of California, Berkeley, CA 94720"},{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101011-155807"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0171-x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00438-7"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab197"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2022.101912"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062917-011816"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.095"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2102683118"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2019.02.001"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00808"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-021-00399-3"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90255-0"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80920-4"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.12.006"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.07.035"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-112618-043633"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14450"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.08.004"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5421.1800"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.5.1019"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1736"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2016011"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.041"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05338"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1751109"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23645"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092938"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315793110"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17365"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/15.7.563"},{"key":"e_1_3_4_31_2","first-page":"28","article-title":"Fitting 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Ptashne, A Genetic Switch: Phage Lambda and Higher Organisms (Cell Press: Blackwell Scientific Publications, Cambridge, MA, ed. 2, 1992), pp. 1\u201333.","edition":"2"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301775"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","unstructured":"N. Fuda . Data from \u201cCombinatorial clustering of distinct DNA motifs directs synergistic binding of\u00a0 C. elegans \u00a0dosage compensation complex to X chromosomes.\u201d https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE205949. Deposited 10\u00a0June 2022.","DOI":"10.1073\/pnas.2211642119"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2211642119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T03:20:26Z","timestamp":1676690426000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2211642119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":38,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2022,9,13]]}},"alternative-id":["10.1073\/pnas.2211642119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2211642119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]},"assertion":[{"value":"2022-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2211642119"}}