title: Arid3b Is Critical for B Lymphocyte Development.
abstract: Arid3a and Arid3b belong to a subfamily of ARID (AT-rich interaction domain) transcription factors. The Arid family is involved in regulating chromatin accessibility, proliferation, and differentiation. Arid3a and Arid3b are closely related and share a unique REKLES domain that mediates their homo- and hetero-multimerization. Arid3a was originally isolated as a B cell transcription factor binding to the AT rich matrix attachment regions (MARS) of the immunoglobulin heavy chain intronic enhancer. Deletion of Arid3a results in a highly penetrant embryonic lethality with severe defects in erythropoiesis and hematopoietic stem cells (HSCs). The few surviving Arid3a-/- (<1%) animals have decreased HSCs and early progenitors in the bone marrow, but all mature lineages are normally represented in the bone marrow and periphery except for B cells. Arid3b-/- animals die around E7.5 precluding examination of hematopoietic development. So it is unclear whether the phenotype of Arid3a loss on hematopoiesis is dependent or independent of Arid3b. In this study we circumvented this limitation by also examining hematopoiesis in mice with a conditional allele of Arid3b. Bone marrow lacking Arid3b shows decreased common lymphoid progenitors (CLPs) and downstream B cell populations while the T cell and myeloid lineages are unchanged, reminiscent of the adult hematopoietic defect in Arid3a mice. Unlike Arid3a-/- mice, HSC populations are unperturbed in Arid3b-/- mice. This study demonstrates that HSC development is independent of Arid3b, whereas B cell development requires both Arid3a and Arid3b transcription factors.
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.|Harper Cancer Research Institute, South Bend, Indiana, United States of America.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Kurkewich
authors.affiliation: Harper Cancer Research Institute, South Bend, Indiana, United States of America.|Department of Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors.forename: Nathan
authors.initials: N
authors.lastname: Klopfenstein
authors.affiliation: Harper Cancer Research Institute, South Bend, Indiana, United States of America.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors.forename: William M
authors.initials: WM
authors.lastname: Hallas
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.|Harper Cancer Research Institute, South Bend, Indiana, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Wood
authors.affiliation: Harper Cancer Research Institute, South Bend, Indiana, United States of America.|Deparment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Sattler
authors.affiliation: Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Chhaya
authors.initials: C
authors.lastname: Das
authors.affiliation: Institute for Cellular and Molecular Biology, Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America.
authors.forename: Haley
authors.initials: H
authors.lastname: Tucker
authors.affiliation: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.|Harper Cancer Research Institute, South Bend, Indiana, United States of America.|Department of Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Harper Cancer Research Institute, South Bend, Indiana, United States of America.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana, United States of America.|Deparment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Cowden Dahl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C510769:Arid3b protein, mouse; D004268:DNA-Binding Proteins; D008156:Luciferases