First Author | Pajerowski AG | Year | 2009 |
Journal | Immunity | Volume | 30 |
Issue | 5 | Pages | 696-707 |
PubMed ID | 19409814 | Mgi Jnum | J:165961 |
Mgi Id | MGI:4839038 | Doi | 10.1016/j.immuni.2009.02.011 |
Citation | Pajerowski AG, et al. (2009) NKAP is a transcriptional repressor of notch signaling and is required for T cell development. Immunity 30(5):696-707 |
abstractText | T cell development depends on the coordinated interplay between receptor signaling and transcriptional regulation. Through a genetic complementation screen a transcriptional repressor, NKAP, was identified. NKAP associated with the histone deacetylase HDAC3 and was shown to be part of a DNA-binding complex, as demonstrated by chromatin immunoprecipitation. NKAP also associated with the Notch corepressor complex. The expression of NKAP during T cell development inversely correlated with the expression of Notch target genes, implying that NKAP may modulate Notch-mediated transcription. To examine the function of NKAP in T cell development, we ablated NKAP by Lck(cre). Loss of NKAP blocked development of alphabeta but not gammadelta T cells, and Nkap(fl/o)Lck(cre) DP T cells expressed 8- to 20-fold higher amounts of Hes1, Deltex1, and CD25 mRNA. Thus, NKAP functions as a transcriptional repressor, acting on Notch target genes, and is required for alphabeta T cell development. |