biostudies-literatureTusi BKCancer Research UKNIAID NIH HHSNHLBI NIH HHSNational Institutes of Health1505-15https://www.ebi.ac.uk/biostudies/studies/S-EPMC4396605biostudies-literatureUnknown29(4)SETD1A is a member of trithorax-related histone methyltransferases that methylate lysine 4 at histone H3 (H3K4). We showed previously that Setd1a is required for mesoderm specification and hematopoietic lineage differentiation in vitro. However, it remains unknown whether or not Setd1a controls specific hematopoietic lineage commitment and differentiation during animal development. Here, we reported that homozygous Setd1a knockout (KO) mice are embryonic lethal. Loss of the Setd1a gene in the hematopoietic compartment resulted in a blockage of the progenitor B-cell-to-precursor B-cell development in bone marrow (BM) and B-cell maturation in spleen. The Setd1a-cKO (conditional knockout) mice exhibited an enlarged spleen with disrupted spleen architecture and leukocytopenia. Mechanistically,FASEB journal : official publication of the Federation of American Societies for Experimental BiologySetd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement.PMC4396605R01 HL090589R01HL09058916753R01 AI058150R01HL095674R01 HL091929R01HL091929R01 HL095674Qiu YDeng CLi YHuang STusi BKZeumer LSalz TSo CWMorel LMfalseSetd1a regulates progenitor B-cell-to-precursor B-cell development through histone H3 lysine 4 trimethylation and Ig heavy-chain rearrangement.SETD1A is a member of trithorax-related histone methyltransferases that methylate lysine 4 at histone H3 (H3K4). We showed previously that Setd1a is required for mesoderm specification and hematopoietic lineage differentiation in vitro. However, it remains unknown whether or not Setd1a controls specific hematopoietic lineage commitment and differentiation during animal development. Here, we reported that homozygous Setd1a knockout (KO) mice are embryonic lethal. Loss of the Setd1a gene in the hematopoietic compartment resulted in a blockage of the progenitor B-cell-to-precursor B-cell development in bone marrow (BM) and B-cell maturation in spleen. The Setd1a-cKO (conditional knockout) mice exhibited an enlarged spleen with disrupted spleen architecture and leukocytopenia. Mechanistically,2015-01-01T00:00:00Z2015 Apr2025-04-18T17:30:12.652Z2019-03-26T23:55:41ZS-EPMC43966052555047110.1096/fj.14-263061