an unexpected function of the prader-willi syndrome imprinting center in maternal imprinting in mice氏综合症印记中心的一个意想不到的功能在老鼠的母本印记.pdfVIP

An Unexpected Function of the Prader-Willi Syndrome Imprinting Center in Maternal Imprinting in Mice 1 1 2 2 1 Mei-Yi Wu *, Ming Jiang , Xiaodong Zhai , Arthur L. Beaudet , Ray-Chang Wu * 1 Department of Biochemistry and Molecular Biology, George Washington University, Washington, District of Columbia, United States of America, 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America Abstract Genomic imprinting is a phenomenon that some genes are expressed differentially according to the parent of origin. Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurobehavioral disorders caused by deficiency of imprinted gene expression from paternal and maternal chromosome 15q11–q13, respectively. Imprinted genes at the PWS/AS domain are regulated through a bipartite imprinting center, the PWS-IC and AS-IC. The PWS-IC activates paternal-specific gene expression and is responsible for the paternal imprint, whereas the AS-IC functions in the maternal imprint by allele-specific repression of the PWS-IC to prevent the paternal imprinting program. Although mouse chromosome 7C has a conserved PWS/AS imprinted domain, the mouse equivalent of the human AS-IC element has not yet been identified. Here, we suggest another dimension that the PWS-IC also functions in maternal imprinting by negatively regulating the paternally expressed imprinted genes in mice, in contrast to its known function as a positive regulator for paternal-specific gene expression. Using a mouse model carrying a 4.8-kb deletion at the PWS-IC, we demonstrated that maternal transmission of the PWS-IC deletion resulted in a maternal imprinting defect with activation of the paternally expressed i