○Takehide Murata Chunyuan Jin Hideyo Ugai Jianzhi Pan Yoriko Shinozuka Kazunari K. Yokoyama
Gene Engineering Div., RIKEN BRC
Differentiation of embryonal calcinoma F9 cells to endoderm by retinoic acid (RA) and by E1A of adenovirus is triggered by the enhanced expression of c-jun. We have identified the Differentiation Responsive Element (DRE) in c-jun promoter, which has a critical role for the regulation of expression of c-jun gene. We also identify the Differentiation Regulatory Factors (DRF) which bound DRE in the c-jun promoter. Jun dimerization protein 2 (JDP2), which is a novel member of AP-1 is included in this DRF and represses a variety of transcriptional response that are associated with Jun/Fos/ATF family. Recent study showed that forced expression of JDP2 prevent differentiation of F9 cells induced by RA and that the transcriptional repression by JDP2 was performed at least in part by recruitment of histone deacetylase 3 complex to the promoter region of the target genes (FEBS Lett. 489: 34, 2001; Mol. Cell. Biol. 22: 4815, 2002). We present here that JDP2 has an inhibitory activity of acetylation of all core histones induced by either p300 or PCAF in vitro. The maximal repression of JDP2 was obtained in the case of preincubation of JDP2 with histones relieved the JDP2- mediated inhibition of histone acetylation (HAT), suggesting JDP2 might target histone itself. Furthermore, we determine both histone-binding and HAT inhibitory domains of JDP2, indicating that the binding domain alone to histones is not sufficient for the ability of JDP2 to inhibit the HAT activity.
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