Novel INHAT repressor (NIR) is required for early lymphocyte development

Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13930-5. doi: 10.1073/pnas.1310118111. Epub 2014 Sep 8.

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.

Keywords: apoptosis; cell cycle; transcription.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • DNA Breaks
  • Mice
  • Precursor Cells, B-Lymphoid / cytology
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Thymocytes / cytology
  • Thymocytes / immunology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / immunology

Substances

  • Antigens, Differentiation
  • NIR protein, mouse
  • Repressor Proteins
  • Tumor Suppressor Protein p53