Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA.
Nucleic Acids Res. 2018 Sep 28;46(17):8848-8864. doi: 10.1093/nar/gky595.
Polycomb group (PcG) and Trithorax group (TrxG) proteins are essential for maintaining epigenetic memory in both embryonic stem cells and differentiated cells. To date, how they are localized to hundreds of specific target genes within a vertebrate genome had remained elusive. Here, by focusing on short cis-acting DNA elements of single functions, we discovered three classes of response elements in human genome: Polycomb response elements (PREs), Trithorax response elements (TREs) and Polycomb/Trithorax response elements (P/TREs). In particular, the four PREs (PRE14, 29, 39 and 48) are the first set of, to our knowledge, bona fide vertebrate PREs ever discovered, while many previously reported Drosophila or vertebrate PREs are likely P/TREs. We further demonstrated that YY1 and CpG islands are specifically enriched in the four TREs (PRE30, 41, 44 and 55), but not in the PREs. The three classes of response elements as unraveled in this study should guide further global investigation and open new doors for a deeper understanding of PcG and TrxG mechanisms in vertebrates.
多梳组 (PcG) 和三价组 (TrxG) 蛋白对于维持胚胎干细胞和分化细胞中的表观遗传记忆至关重要。迄今为止，它们如何定位于脊椎动物基因组中的数百个特定靶基因仍然难以捉摸。在这里，我们通过专注于单一功能的短顺式作用 DNA 元件，在人类基因组中发现了三类反应元件：多梳反应元件 (PREs)、三价组反应元件 (TREs) 和多梳/三价组反应元件 (P/TREs)。特别是，四个 PREs (PRE14、29、39 和 48) 是我们所知的第一组真正的脊椎动物 PREs，而之前报道的许多果蝇或脊椎动物 PREs 可能是 P/TREs。我们进一步证明 YY1 和 CpG 岛在四个 TREs (PRE30、41、44 和 55) 中特异性富集，但在 PREs 中没有富集。本研究中揭示的这三类反应元件应指导进一步的全球研究，并为深入了解脊椎动物中的 PcG 和 TrxG 机制开辟新的途径。
