title: Novel INHAT repressor (NIR) is required for early lymphocyte development.
abstract: Novel inhibitor of histone acetyltransferase repressor (NIR) is a transcriptional corepressor with inhibitor of histone acetyltransferase activity and is a potent suppressor of p53. Although NIR deficiency in mice leads to early embryonic lethality, lymphoid-restricted deletion resulted in the absence of double-positive CD4(+)CD8(+) thymocytes, whereas bone-marrow-derived B cells were arrested at the B220(+)CD19(-) pro-B-cell stage. V(D)J recombination was preserved in NIR-deficient DN3 double-negative thymocytes, suggesting that NIR does not affect p53 function in response to physiologic DNA breaks. Nevertheless, the combined deficiency of NIR and p53 provided rescue of DN3L double-negative thymocytes and their further differentiation to double- and single-positive thymocytes, whereas B cells in the marrow further developed to the B220(+)CD19(+) pro-B-cell stage. Our results show that NIR cooperate with p53 to impose checkpoint for the generation of mature B and T lymphocytes.
authors.affiliation: Clinical Immunology Unit, Laboratory of Host Defenses.
authors.forename: Chi A
authors.initials: CA
authors.lastname: Ma
authors.affiliation: Clinical Immunology Unit, Laboratory of Host Defenses.
authors.forename: Antonia
authors.initials: A
authors.lastname: Pusso
authors.affiliation: Clinical Immunology Unit, Laboratory of Host Defenses.
authors.forename: Liming
authors.initials: L
authors.lastname: Wu
authors.affiliation: Clinical Immunology Unit, Laboratory of Host Defenses.
authors.forename: Yongge
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Diagnostic and Research Services Branch, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hoffmann
authors.affiliation: Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, and.
authors.forename: B J
authors.initials: BJ
authors.lastname: Fowlkes
authors.affiliation: Clinical Immunology Unit, Laboratory of Host Defenses, ashish.jain1@merck.com.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D053960:DNA Breaks; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; C507221:NIR protein, mouse; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53
keywords: apoptosis; cell cycle; transcription