The imprinting mechanism of the Prader-Willi/Angelman regional control center

被引：72

作者：

Perk, J ^{[1
]}

Makedonski, K ^{[1
]}

Lande, L ^{[1
]}

Cedar, H ^{[1
]}

Razin, A ^{[1
]}

Shemer, R ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel

来源：

EMBO JOURNAL | 2002年 / 21卷 / 21期

关键词：

DNA methylation; DNase sensitivity; histone modification; Prader-Willi; Angelman regional control center;

D O I：

10.1093/emboj/cdf570

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The 2 Mb domain on chromosome 15q11-q13 that carries the imprinted genes involved in Prader-Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS-SRO located around the SNRPN promoter and the AS-SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS-SRO is sensitive to DNase I, and packaged with acetylated histone H4 and methylated histone H3(K4) only on the maternal allele, and this imprinted epigenetic structure is maintained in dividing cells despite the absence of clearcut differential DNA methylation. Genetic analysis shows that the maternal AS-SRO is essential for setting up the DNA methylation state and closed chromatin structure of the neighboring PWS-SRO. In contrast, the PWS-SRO has no influence on the epigenetic features of the AS-SRO. These results suggest a stepwise, unidirectional program in which structural imprinting at the AS-SRO brings about allele-specific repression of the maternal PWS-SRO, thereby preventing regional activation of genes on this allele.

引用

页码：5807 / 5814

页数：8

共 35 条

[1] De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch [J].