Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden.
Nucleic Acids Res. 2023 Nov 27;51(21):11613-11633. doi: 10.1093/nar/gkad889.
Development of multicellular animals requires epigenetic repression by Polycomb group proteins. The latter assemble in multi-subunit complexes, of which two kinds, Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2), act together to repress key developmental genes. How PRC1 and PRC2 recognize specific genes remains an open question. Here we report the identification of several hundreds of DNA elements that tether canonical PRC1 to human developmental genes. We use the term tether to describe a process leading to a prominent presence of canonical PRC1 at certain genomic sites, although the complex is unlikely to interact with DNA directly. Detailed analysis indicates that sequence features associated with PRC1 tethering differ from those that favour PRC2 binding. Throughout the genome, the two kinds of sequence features mix in different proportions to yield a gamut of DNA elements that range from those tethering predominantly PRC1 or PRC2 to ones capable of tethering both complexes. The emerging picture is similar to the paradigmatic targeting of Polycomb complexes by Polycomb Response Elements (PREs) of Drosophila but providing for greater plasticity.
多细胞动物的发育需要表观遗传抑制 Polycomb 组蛋白。后者组装成多亚基复合物，其中两种类型，多梳抑制复合物 1（PRC1）和多梳抑制复合物 2（PRC2），共同作用抑制关键的发育基因。PRC1 和 PRC2 如何识别特定基因仍然是一个悬而未决的问题。在这里，我们报告了几种数百个 DNA 元件的鉴定，这些元件将典型的 PRC1 固定在人类发育基因上。我们使用“固定”一词来描述一个过程，导致典型的 PRC1 在某些基因组位点上的明显存在，尽管该复合物不太可能直接与 DNA 相互作用。详细分析表明，与 PRC2 结合相比，与 PRC1 固定相关的序列特征不同。在整个基因组中，这两种序列特征以不同的比例混合，产生一系列 DNA 元件，从主要固定 PRC1 或 PRC2 的元件到能够固定两个复合物的元件。这种新出现的情况类似于多梳复合物由果蝇的多梳反应元件（PREs）靶向，但提供了更大的灵活性。
