BFL综合症蛋白PHF6调控摄食与肥胖的分子机制

Börjeson-Forssman-Lehmann （BFL）综合症是一种以智力障碍合并肥胖等代谢障碍为特征的神经系统疾病。BFL综合症蛋白Plant Homeodomain Finger Protein 6（PHF6）是一种染色质结合蛋白。本项目旨在研究PHF6调控摄食和代谢的分子机制，通过探索PHF6在下丘脑神经元和垂体内分泌细胞中的功能作用，理解PHF6缺失或突变造成肥胖表型的致病机理。分子机制上，我们将通过IP-MS探索PHF6与哪些蛋白或蛋白复合体发生相互作用，通过细胞类型特异性的RNA-seq、ChIP-seq、ATAC-seq和Hi-C探索PHF6动态调控染色质结构、表观遗传修饰、以及下游基因转录调控的分子机制。在基因组水平解析PHF6对染色质三维结构和区域排列的动态调控作用，可以帮助我们深入理解BFL综合症蛋白PHF6调控摄食与肥胖的分子机理。

Börjeson-Forssman-Lehmann syndrome (BFLS) is a neural disorder characterized with mental retardation and obesity. BFL syndrome protein PHF6 is a chromatin binding protein. We aim to understand the molecular mechanism of PHF6 in the regulation of feeding and metabolism. In the hypothalamic neurons and the pituitary endocrine cells, we want to understand the causal relationship between the PHF6 loss and the obesity phenotype in BFL syndrome. Mechanistically, we want to identify the interacting proteins or complex of PHF6 in the brain. Through cell-type specific RNA-seq, ChIP-seq, ATAC-seq and Hi-C analyses, we want to understand how PHF6 influences the chromatin structure, epigenetic modifications, and transcriptional regulation. Genome-widely characterizing the role of PHF6 in regulating the chromatin 3D structure dynamics and topologically associated domains will shed light on our understanding of the functional role of PHF6 and the molecular mechanism of BFL syndrome.