{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:30:10Z","timestamp":1786591810586,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,10]]},"group-title":"Cell Biology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA233749"],"award-info":[{"award-number":["R01CA233749"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  MLLT1 (also named ENL) is a chromatin reader protein whose encoding gene was originally identified as a chromosomal translocation partner with\n                  <jats:italic>MLL<\/jats:italic>\n                  (\n                  <jats:italic>KMT2A<\/jats:italic>\n                  ) in acute leukemia. However, its role in normal hematopoiesis has not been investigated. This study uncovers a critical role of Mllt1 in normal B cell lymphopoiesis. We found Mllt1 to be essential for early B lymphocyte development using a conditional\n                  <jats:italic>Mllt1<\/jats:italic>\n                  knockout mouse model that we developed. A significant decrease of bone marrow B-lineage progenitors, splenic transitional B cells and peripheral blood B cells were observed in\n                  <jats:italic>\n                    Mllt1\n                    <jats:sup>del<\/jats:sup>\n                  <\/jats:italic>\n                  mice compared to control\n                  <jats:italic>\n                    Mllt1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                  <\/jats:italic>\n                  mice. Similarly,\n                  <jats:italic>Mllt1<\/jats:italic>\n                  deletion in\n                  <jats:italic>in vitro<\/jats:italic>\n                  cultured B-enriched progenitor cells from\n                  <jats:italic>\n                    Mllt1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    ; Rosa26CreER\n                    <jats:sup>T2\/+<\/jats:sup>\n                  <\/jats:italic>\n                  mice resulted in reduced B cells, demonstrating the cell-intrinsic role of\n                  <jats:italic>Mllt1<\/jats:italic>\n                  in this process. Direct MLLT1 target genes including\n                  <jats:italic>Il7r<\/jats:italic>\n                  and critical B-lineage transcription factors,\n                  <jats:italic>Ebf1<\/jats:italic>\n                  and\n                  <jats:italic>Pax5<\/jats:italic>\n                  , were decreased following\n                  <jats:italic>Mllt1<\/jats:italic>\n                  deletion. Gene set enrichment, gene ontology, and functional analyses of\n                  <jats:italic>Mllt1<\/jats:italic>\n                  -deficient cells showed significant alterations related to B cell development, critical relevant signaling pathways, DNA replication, and mitochondrial function.\n                  <jats:italic>In vitro<\/jats:italic>\n                  complementation with\n                  <jats:italic>MLLT1<\/jats:italic>\n                  rescued the B cell phenotype observed with endogenous\n                  <jats:italic>Mllt1<\/jats:italic>\n                  deletion; however, specific MLLT1 YEATS domain mutants lacking chromatin reader and RNA-binding functions were unable to rescue the phenotype. Taken together, our research demonstrates a previously unappreciated role for MLLT1 as critical for maintenance of B cell lymphopoiesis.\n                <\/jats:p>","DOI":"10.64898\/2026.08.08.743534","type":"posted-content","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:45:11Z","timestamp":1786376711000},"source":"Crossref","is-referenced-by-count":0,"title":["The chromatin reader protein MLLT1 is critical to maintain normal B lymphopoiesis"],"prefix":"10.64898","author":[{"given":"Janani","family":"Prakash","sequence":"first","affiliation":[{"name":"Integrative Cell Biology Program, Loyola University Chicago, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Achille","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Loyola University Chicago, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3429-0803","authenticated-orcid":false,"given":"Emmalee R.","family":"Adelman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, 33136"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Loyola University Chicago, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5386-1758","authenticated-orcid":false,"given":"John H.","family":"Bushweller","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22903"},{"name":"Department of Chemistry, University of Virginia, Charlottesville, VA 22904"},{"name":"University of Virginia NCI-designated Comprehensive Cancer Center, Charlottesville, VA 22903"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL, 33136"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-9273","authenticated-orcid":false,"given":"Charles S.","family":"Hemenway","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Louisiana State University Health Sciences Center"},{"name":"Center for Cancer and Blood Disorders, Manning Family Children\u2019s, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2432-9892","authenticated-orcid":false,"given":"Nancy J.","family":"Zeleznik-Le","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Loyola University Chicago, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081220051659000_2026.08.08.743534v1.1","doi-asserted-by":"publisher","DOI":"10.1139\/O08-111"},{"key":"2026081220051659000_2026.08.08.743534v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2023.06.001"},{"key":"2026081220051659000_2026.08.08.743534v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.135"},{"key":"2026081220051659000_2026.08.08.743534v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature21688"},{"key":"2026081220051659000_2026.08.08.743534v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature21687"},{"issue":"6","key":"2026081220051659000_2026.08.08.743534v1.6","doi-asserted-by":"crossref","first-page":"117540","DOI":"10.1016\/j.celrep.2026.117540","article-title":"The MLLT3 YEATS domain binds histone marks (H3KS\/18\/27ac\/cr) and ncRNA (7SK), linking transcription and RNA signaling to regulate hematopoiesis","volume":"45","year":"2026","journal-title":"Cell Rep"},{"key":"2026081220051659000_2026.08.08.743534v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.11.011"},{"key":"2026081220051659000_2026.08.08.743534v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2014.08.010"},{"key":"2026081220051659000_2026.08.08.743534v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.004"},{"key":"2026081220051659000_2026.08.08.743534v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204478"},{"key":"2026081220051659000_2026.08.08.743534v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.12.040"},{"key":"2026081220051659000_2026.08.08.743534v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1790-2"},{"key":"2026081220051659000_2026.08.08.743534v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad993"},{"key":"2026081220051659000_2026.08.08.743534v1.14","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2002.0525"},{"issue":"13","key":"2026081220051659000_2026.08.08.743534v1.15","doi-asserted-by":"crossref","first-page":"111019","DOI":"10.1016\/j.celrep.2022.111019","article-title":"BAFFR activates PI3K\/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors","volume":"39","year":"2022","journal-title":"Cell Rep"},{"key":"2026081220051659000_2026.08.08.743534v1.16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02285"},{"key":"2026081220051659000_2026.08.08.743534v1.17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092210"},{"key":"2026081220051659000_2026.08.08.743534v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/nature02284"},{"key":"2026081220051659000_2026.08.08.743534v1.19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91406"},{"issue":"2","key":"2026081220051659000_2026.08.08.743534v1.20","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1158\/2643-3230.BCD-20-0036","article-title":"BCOR Binding to MLL-AFS Is Essential for Leukemia via Altered EYA1","volume":"1","year":"2020","journal-title":"SIX, and MYC Activity. Blood Cancer Discov"},{"key":"2026081220051659000_2026.08.08.743534v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.03.028"},{"key":"2026081220051659000_2026.08.08.743534v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.049"},{"key":"2026081220051659000_2026.08.08.743534v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.003"},{"key":"2026081220051659000_2026.08.08.743534v1.24","doi-asserted-by":"crossref","unstructured":"Fedl, A.S. , et al., Transcriptional function of E2A, Ebf1, Pax5, Ikaros and Aiolos analyzed by in vivo acute protein degradation in early B cell development. Nat Immunol, 2024. 25(9): p. 1663-1677.","DOI":"10.1038\/s41590-024-01933-7"},{"key":"2026081220051659000_2026.08.08.743534v1.25","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.24.8539-8551.2002"},{"key":"2026081220051659000_2026.08.08.743534v1.26","doi-asserted-by":"crossref","unstructured":"Zolotarev, N. , M. Bayer , and R. Grosschedl , EBF1 is continuously required for stabilizing local chromatin accessibility in pro-B cells. Proc Natl Acad Sci U S A, 2022. 119(48): p. e2210595119.","DOI":"10.1073\/pnas.2210595119"},{"key":"2026081220051659000_2026.08.08.743534v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.019"},{"key":"2026081220051659000_2026.08.08.743534v1.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211427109"},{"key":"2026081220051659000_2026.08.08.743534v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1891"},{"key":"2026081220051659000_2026.08.08.743534v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nri3570"},{"key":"2026081220051659000_2026.08.08.743534v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.11.002"},{"issue":"5","key":"2026081220051659000_2026.08.08.743534v1.32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/14779072.2017.1319278","article-title":"Eat, breathe, ROS: controlling stem cell fate through metabolism","volume":"15","year":"2017","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"2026081220051659000_2026.08.08.743534v1.33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.9.4431"},{"issue":"5","key":"2026081220051659000_2026.08.08.743534v1.34","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/imcb.12030","article-title":"Molecular control of B-cell homeostasis in health and malignancy","volume":"96","year":"2018","journal-title":"Immunol Cell Biol"},{"key":"2026081220051659000_2026.08.08.743534v1.35","first-page":"77","article-title":"B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback Exerted by Mature B Cells","volume":"7","year":"2016","journal-title":"Front Immunol"},{"key":"2026081220051659000_2026.08.08.743534v1.36","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20180565"},{"key":"2026081220051659000_2026.08.08.743534v1.37","doi-asserted-by":"crossref","unstructured":"Lin, H. and R. Grosschedl , Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature, 1995. 376(6537): p. 263-7.","DOI":"10.1038\/376263a0"},{"key":"2026081220051659000_2026.08.08.743534v1.38","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090756"},{"key":"2026081220051659000_2026.08.08.743534v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.140"},{"key":"2026081220051659000_2026.08.08.743534v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16828-y"},{"key":"2026081220051659000_2026.08.08.743534v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.155"},{"key":"2026081220051659000_2026.08.08.743534v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.4.1745"},{"issue":"1","key":"2026081220051659000_2026.08.08.743534v1.43","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4049\/jimmunol.146.1.350","article-title":"The expression of the Ig H chain repertoire in developing bone marrow B lineage cells","volume":"146","year":"1991","journal-title":"J Immunol"},{"key":"2026081220051659000_2026.08.08.743534v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00543.x"},{"key":"2026081220051659000_2026.08.08.743534v1.45","doi-asserted-by":"publisher","DOI":"10.1101\/gad.291504"},{"key":"2026081220051659000_2026.08.08.743534v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1612"},{"key":"2026081220051659000_2026.08.08.743534v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.10.003"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.08.743534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:05:27Z","timestamp":1786590327000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.08.08.743534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":47,"URL":"https:\/\/doi.org\/10.64898\/2026.08.08.743534","relation":{},"subject":[],"published":{"date-parts":[[2026,8,10]]},"subtype":"preprint"}}