Beuchle D, Struhl G, Müller J
Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35/III, 72076 Tübingen, Germany.
Development. 2001 Mar;128(6):993-1004. doi: 10.1242/dev.128.6.993.
Early in Drosophila embryogenesis, transcriptional repressors encoded by Gap genes prevent the expression of particular combinations of Hox genes in each segment. During subsequent development, those Hox genes that were initially repressed in each segment remain off in all the descendent cells, even though the Gap repressors are no longer present. This phenomenon of heritable silencing depends on proteins of the Polycomb Group (PcG) and on cis-acting Polycomb response elements (PREs) in the Hox gene loci. We have removed individual PcG proteins from proliferating cells and then resupplied these proteins after a few or several cell generations. We show that most PcG proteins are required throughout development: when these proteins are removed, Hox genes become derepressed. However, we find that resupply of at least some PcG proteins can cause re-repression of Hox genes, provided that it occurs within a few cell generations of the loss of repression. These results suggest a functional distinction between transcriptional repression and heritable silencing: in at least some contexts, Hox genes can retain the capacity to be heritably silenced, despite being transcribed and replicated. We propose that silenced Hox genes bear a heritable, molecular mark that targets them for transcriptional repression. Some PcG proteins may be required to define and propagate this mark; others may function to repress the transcription of Hox genes that bear the mark.
在果蝇胚胎发育早期，间隙基因编码的转录抑制因子可阻止每个体节中特定组合的Hox基因表达。在随后的发育过程中，那些最初在每个体节中被抑制的Hox基因在所有后代细胞中都保持关闭状态，即使间隙抑制因子不再存在。这种可遗传沉默的现象依赖于多梳家族（PcG）的蛋白质以及Hox基因座中的顺式作用多梳反应元件（PREs）。我们从增殖细胞中去除了单个的PcG蛋白，然后在几个或几个细胞世代后重新提供这些蛋白。我们发现，大多数PcG蛋白在整个发育过程中都是必需的：当去除这些蛋白时，Hox基因会去抑制。然而，我们发现，至少重新提供一些PcG蛋白能够导致Hox基因重新被抑制，前提是在抑制丧失后的几个细胞世代内发生重新提供。这些结果表明转录抑制和可遗传沉默之间存在功能差异：在至少某些情况下，Hox基因尽管被转录和复制，但仍能保留可遗传沉默的能力。我们提出，沉默的Hox基因带有一种可遗传的分子标记，该标记将它们靶向用于转录抑制。可能需要一些PcG蛋白来定义和传播这种标记；其他蛋白可能起到抑制带有该标记的Hox基因转录的作用。
