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Figure 8


Fig. 8. GNL3L suppresses SRC-mediated transcriptional coactivation of ERR{gamma}. (A) Using the same cell-based reporter system as described in Fig. 4, we show that the ERE-specific transcriptional activity in cells coexpressing ERR{gamma} and SRC1 (8.0±0.3) is 1.7 times higher than that of the ERR{gamma}-expressing sample (4.8±0.3). When coexpressed with the wild-type GNL3L (WT), this ERR{gamma} and SRC1-mediated ERE-specific transcriptional activity is reduced by 55% and 70% compared with the sample expressing both ERR{gamma} and SRC1 in a dose-dependent manner. This inhibitory effect of GNL3L on the SRC1-mediated coactivation of ERR{gamma} requires the I-domain of GNL3L because deletion of this domain (dI) fails to suppress the transcriptional activity of ERR{gamma} and SRC1 (P=0.17). (B) Using the same approach, we show that GNL3L can also suppress the coactivator function of SRC2 on the ERR{gamma}-dependent transcriptional activity in a dose-dependent (54% reduction for 100 ng of GNL3L and 71% reduction for 200 ng of GNL3L) and I-domain-dependent (P=0.58) manner. Error bars represent the stand error of mean (± s.e.m.). ***P<0.0001.