Strouboulis J, Damjanovski S, Vermaak D, Meric F, Wolffe A P
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5431, USA.
Mol Cell Biol. 1999 Jun;19(6):3958-68. doi: 10.1128/MCB.19.6.3958.
The Polycomb group (Pc-G) genes encode proteins that assemble into complexes implicated in the epigenetic maintenance of heritable patterns of expression of developmental genes, a function largely conserved from Drosophila to mammals and plants. The Pc-G is thought to act at the chromatin level to silence expression of target genes; however, little is known about the molecular basis of this repression. In keeping with the evidence that Pc-G homologs in higher vertebrates exist in related pairs, we report here the isolation of XPc1, a second Polycomb homolog in Xenopus laevis. We show that XPc1 message is maternally deposited in a translationally masked form in Xenopus oocytes, with XPc1 protein first appearing in embryonic nuclei shortly after the blastula stage. XPc1 acts as a transcriptional repressor in vivo when tethered to a promoter in Xenopus embryos. We find that XPc1-mediated repression can be only partially alleviated by an increase in transcription factor dosage and that inhibition of deacetylase activity by trichostatin A treatment has no effect on XPc1 repression, suggesting that histone deacetylation does not form the basis for Pc-G-mediated repression in our assay.
多梳蛋白家族(Pc-G)基因编码的蛋白质可组装成复合物,参与发育基因可遗传表达模式的表观遗传维持,从果蝇到哺乳动物和植物,这一功能在很大程度上是保守的。Pc-G被认为在染色质水平发挥作用,使靶基因沉默;然而,对于这种抑制作用的分子基础知之甚少。鉴于高等脊椎动物中的Pc-G同源物以相关对的形式存在这一证据,我们在此报告非洲爪蟾中第二个多梳蛋白同源物XPc1的分离。我们表明,XPc1信使RNA以翻译抑制的形式母源性地沉积在非洲爪蟾卵母细胞中,XPc1蛋白在囊胚期后不久首次出现在胚胎细胞核中。当与非洲爪蟾胚胎中的启动子相连时,XPc1在体内作为转录抑制因子起作用。我们发现,转录因子剂量的增加只能部分缓解XPc1介导的抑制作用,曲古抑菌素A处理对脱乙酰酶活性的抑制对XPc1抑制作用没有影响,这表明在我们的实验中,组蛋白去乙酰化不是Pc-G介导的抑制作用的基础。