Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Sci Adv. 2019 Jan 9;5(1):eaau9739. doi: 10.1126/sciadv.aau9739. eCollection 2019 Jan.
Polycomb group proteins (PcGs) drive target gene repression and form large chromatin domains. In , DNA elements known as Polycomb group response elements (PREs) recruit PcGs to the DNA. We have shown that, within the (-) Polycomb domain, strong, constitutive PREs are dispensable for Polycomb domain structure and function. We suggest that the endogenous chromosomal location imparts stability to this Polycomb domain. To test this possibility, a 79-kb transgene was inserted into other chromosomal locations. This transgene is functional and forms a Polycomb domain. The spreading of the H3K27me3 repressive mark, characteristic of PcG domains, varies depending on the chromatin context of the transgene. Unlike at the endogenous locus, deletion of the strong, constitutive PREs from the transgene leads to both loss- and gain-of function phenotypes, demonstrating the important role of these regulatory elements. Our data show that chromatin context plays an important role in Polycomb domain structure and function.
多梳抑制复合物蛋白（PcGs）驱动靶基因抑制，并形成大的染色质域。在 中，被称为多梳抑制复合物反应元件（PREs）的 DNA 元件将 PcGs 招募到 DNA 上。我们已经表明，在 (-)多梳抑制复合物域内，强的、组成性的 PREs 对于多梳抑制复合物域的结构和功能是可有可无的。我们认为，内源性染色体位置赋予了这个多梳抑制复合物域稳定性。为了验证这一可能性，我们将一个 79kb 的转基因插入到其他染色体位置。这个转基因是有功能的，并形成一个多梳抑制复合物域。H3K27me3 抑制标记的扩散，这是 PcG 域的特征，取决于转基因的染色质背景。与内源性基因座不同，从转基因中删除强的、组成性的 PREs 会导致功能丧失和获得的表型，这表明这些调节元件的重要作用。我们的数据表明，染色质背景在多梳抑制复合物域的结构和功能中起着重要作用。
