Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India(1).
Gene. 2022 Dec 15;845:146832. doi: 10.1016/j.gene.2022.146832. Epub 2022 Aug 23.
Polycomb and Trithorax group proteins (PcG, TrxG) epigenetically regulate developmental genes. These proteins bind with specific DNA elements, the Polycomb Response Element (PRE). Apart from mutations in polycomb/ trithorax proteins, altered cis-elements like PRE underlie the modified function and thus disease etiology. PREs are well studied in Drosophila, while only a few human PREs have been reported. We have identified a polycomb responsive DNA element, hPRE-HoxA3, in the intron of the HoxA3 gene. The hPRE-HoxA3 represses luciferase reporter activity in a PcG-dependent manner. The endogenous hPRE-HoxA3 element recruits PcG proteins and is enriched with repressive H3K27me3 marks, demonstrating that hPRE-HoxA3 is a part of the PcG-dependent gene regulatory network. Furthermore, it interacts with D11-12, the well-known PRE in the human Hox cluster. hPRE-Hox3 is a part of the 3-dimensional chromosomal domain organization as it is involved in the long-range interaction with other PcG enriched regions of Hox A, B, C, and D clusters.
多梳和三价组蛋白（PcG、TrxG）通过表观遗传调控发育基因。这些蛋白与特定的 DNA 元件结合，即多梳反应元件（PRE）。除了多梳/三价蛋白的突变外，改变顺式元件如 PRE 也是功能改变的基础，从而导致疾病的病因。PRE 在果蝇中研究得很好，而只有少数人类 PRE 被报道过。我们在 HoxA3 基因的内含子中鉴定出一个多梳反应性 DNA 元件 hPRE-HoxA3。hPRE-HoxA3 以 PcG 依赖性的方式抑制荧光素酶报告基因的活性。内源性 hPRE-HoxA3 元件招募 PcG 蛋白，并富集具有抑制性 H3K27me3 标记，表明 hPRE-HoxA3 是 PcG 依赖性基因调控网络的一部分。此外，它与 D11-12 相互作用，D11-12 是人类 Hox 簇中众所周知的 PRE。hPRE-Hox3 是三维染色体结构域组织的一部分，因为它参与了与 Hox A、B、C 和 D 簇的其他 PcG 富集区域的长距离相互作用。
