人KCNQ1是重要的钾离子通道印迹基因，其印迹丢失在长QT综合征和恶性肿瘤等发生中起重要作用,但人KCNQ1印迹从正常到丢失的转换调控机制仍不清楚，因此开展KCNQ1印迹转换机制研究十分必要。项目组前期研究发现鼠Kcnq1印迹转换受长距离染色体构象调控，在此基础上，课题组认为染色体构象可能在人KCNQ1印迹转换中也起关键调控作用。为此,本项目采用陷阱CTCF重组蛋白，建立了用于人KCNQ1印迹转换机制研究的细胞模型，旨在通过染色体构象捕捉、关联染色体陷阱、染色质免疫共沉淀、DNA亲和吸附洗脱等分子生物学与表观遗传学的技术手段，深入分析人KCNQ1印迹转换中的染色体构象变化和关键表观遗传修饰，辨析关键染色体构象形成因子并揭示其调控KCNQ1印迹转换的能力。相信本项目的开展将有利于深入理解染色体构象在KCNQ1印迹转换中的关键作用，为探寻到新的关键KCNQ1印迹调控因子提供依据。

The human KCNQ1 is an imprinting gene and encodes an important member of potassium voltage-gated channel. Loss of KCNQ1 imprinting (LOI), resulting in bi-allelic KCNQ1 expression and, consequently, transition of KCNQ1 imprinting, play a key role in long QT syndrome and tumorigenesis. However, the mechanism underlying transition of KCNQ1 imprinting remains unclear. We previously revealed that mouse Kcnq1 imprinting was regulated by orchestrating long-range chromatin looping, we thus hypothesized that long-range chromosomal interaction may play a key role in the human KCNQ1 imprinting. To test this hypothesis, we further established human cell model wherein loss of KCNQ1 imprinting can be triggered by decoy CTCF mediated chromatin remodeling. In this project, we plan to explore the molecular basis of chromatin remodeling in aberrant KCNQ1 imprinting and reveal epigenetic modification across KCNQ1 locus. We will also identify key factors that can organize chromatin loops and shed light on its functional role. In conclusion, this project will provide an innovative model to uncover the key role of chromosome conformation in KCNQ1 imprinting, lead the new strategy to identify new imprinting factors and increase the understanding of epigenetic events underlying KCNQ1 imprinting.