Alternative titles; symbols
HGNC Approved Gene Symbol: NOC2L
Cytogenetic location: 1p36.33 Genomic coordinates (GRCh38): 1:944,203-959,256 (from NCBI)
Histone modification by histone acetyltransferases (HAT) and histone deacetylases (HDAC) can control major aspects of transcriptional regulation. NOC2L represents a novel HDAC-independent inhibitor of histone acetyltransferase (INHAT) (Hublitz et al., 2005).
By database analysis to screen for proteins that contain the core SET (600960)/TAF1B (604904) INHAT domain, followed by PCR of a prostate cDNA library, Hublitz et al. (2005) cloned NOC2L, which they called NIR. The 749-amino acid protein contains an N-terminal and a C-terminal INHAT domain, as well as a putative bipartite nuclear localization signal. RT-PCR analysis showed Nir mRNA present at all analyzed stages of mouse embryogenesis. Dot-blot analysis found expression in all human adult tissues tested. Northern blot analysis showed a single 3.3-kb transcript.
By GST pull-down analysis, Hublitz et al. (2005) showed that NIR interacted directly with calf thymus core histones and nucleosomes isolated from HeLa cells. NIR INHAT regions robustly reduced p300 (602700) acetylation of all core histones. NIR repressed basal as well as activated transcription, and HDAC inhibitors did not block NIR-mediated repression of acetylation, showing that NIR functions independent of HDAC activity. Using tandem affinity purification analysis in 293 cells and MALDI-TOF/TOF mass spectrometry analysis, Hublitz et al. (2005) showed that NIR interacted directly with p53 (TP53; 191170). Confocal laser scanning microscopy colocalized endogenous p53 and NIR to the nucleus. Transient transfection experiments showed dose-dependent NIR suppression of a p53-activated reporter and p53-mediated activation of the p21 (116899), PIG3 (605171), and Noxa (604959) promoters. NIR did not block activity of other transcription factors such as CBF1 (147183), androgen receptor (313700), or thyroid hormone receptor (see 190120). Chromatin immunoprecipitation experiments showed that NIR associated with the p21 promoter in a p53-dependent manner. NIR depletion induced p53-dependent apoptosis, demonstrating that NIR is critically involved in regulation of p53-dependent apoptosis.
Hublitz, P., Kunowska, N., Mayer, U. P., Muller, J. M., Heyne. K., Yin, N., Fritzsche, C., Poli, C., Miguet, L., Schupp, I. W., van Grunsven, L. A., Potiers, N., van Dorsselaer, A., Metzger, E., Roemer, K., Schule, R. NIR is a novel INHAT repressor that modulates the transcriptional activity of p53. Genes Dev. 19: 2912-2924, 2005. [PubMed: 16322561] [Full Text: https://doi.org/10.1101/gad.351205]